Platelets are tiny blood cells that prevent injury and infection by forming clots to stop bleeding.
Antiplatelet activity is an action that prevents and treats blood clots.
Anticoagulants, commonly known as blood thinners, are conventional medicines used to reduce the coagulation of blood, prolong the clotting time.
Anticoagulants have been used widely for people with a high risk of heart diseases and stroke due to narrowing arteries associated with plaque accumulation on the arterial walls.
Platelets are made in the bone marrow that also produces white and red blood cells.
Diseases associated with low and abnormal blood platelet include
* Thrombocytopenia is a condition characterized by low blood platelet due to abnormal function of the bone marrow that makes platelets. patients with thrombocytopenia due to the low quantity of blood platelets may experience symptoms of a bruise, internal bleeding, nosebleed.
Long-term untreated thrombocytopenia has been found to increase the risk of cancer, liver disease, pregnancy, infections, and an abnormal immune system.
* Essential thrombocythemia is a disease associated with overproducing blood platelets by the bone marrow, leading to symptoms of blood clots that form and block the blood supply to the brain or the heart.
* Secondary thrombocytosis is also another condition caused by too many platelets produced by the bone marrow.
Angelica or Dang Qui is a herb of Genus Angelica from the family Apiaceae, indigenous to China.
The herb has been used as a Queen herb in traditional Chinese medicine antispasmodic and vasodilatory agent, and to balance the hormones in women for a normal menstrual cycle and menstruation and strengthen heart, spleen, kidneys, and liver for both men and women, etc. In other words, it is used to treat gynecological ailments, fatigue, mild anemia, and high blood pressure. It has analgesic, anti-inflammatory, etc.
On finding a natural compound for the treatment of platelet aggression, the researchers examined the impact of these four commonly used Chinese medicinal herbs on the pharmacokinetics and pharmacodynamics of the combination therapy with clopidogrel and aspirin.
In order to mimic the standard dosing regimen for dual antiplatelet therapy (DAPT) in humans, Sprague-Dawley rats treatment groups were received a bolus oral dose of DAPT on day 1 followed by DAPT for consecutive 13 days in the absence and presence of orally co-administered four TCM herbs (Danshen, Gegen, Danggui, and Chuanxiong) at their low and high doses.
According to the results on day 14, and observed the plasma concentrations of aspirin (ASA) and clopidogrel (CLP) and their corresponding metabolites,
* Co-administration of Gegen and Danggui significantly altered the pharmacokinetics of ASA and CLP in DAPT with increased systemic exposure of ASA and CLP respectively.
Furthermore, DAPT with Danshen, Gegen, and Danggui co-treatment. significant inhibition on rCyp2c11 that enzymes mediate metabolism of ASA and carboxylesterase activities in drug metabolism, compared to a minimal impact on aspirin esterase activity in all co-administered herbs.
Moreover. all DAPT treatment groups showed a significantly longer prothrombin time (PT) compared to a decrease of the DAPT group in presence of Gegen, Danggui, and Chuanxiong with no change to other coagulative expressions.
Taken altogether, Herbal Angelica used combined with other herbal medicine may be used as a remedy to offset the anticoagulant activity of DAPT, pending to larger sample size and multicenter human study.
Natural Medicine for Fatty Liver And Obesity Reversal - The Revolutionary Findings To Achieve Optimal Health And Lose Weight
How To Get Rid Of Eye Floaters
Contrary To Professionals Prediction, Floaters Can Be Cured Naturally
Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You. How-To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months
Back to Kyle J. Norton Homepage http://kylejnorton.blogspot.ca
Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published online, including worldwide health, ezine articles, article base, health blogs, self-growth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bioscience, ISSN 0975-6299.
Sources
(1) Impact of the Chinese herbal medicines on dual antiplatelet therapy with clopidogrel and aspirin: Pharmacokinetics and pharmacodynamics outcomes and related mechanisms in rats by Xiao M1, Qian C2, Luo X3, Yang M4, Zhang Y5, Wu C6, Mok C7, Lee P8, Zuo Z. (PubMed)
Friday, December 24, 2021
Sunday, December 19, 2021
Cranberry Inhibits Neurodegenerative Diseases in Vitro
Age-related neurological disorders or neurodegenerative diseases are the conditions of the progressive death of neuron due to aging, leading to the problems with movement (called ataxias), or mental functioning including Alzheimer's disease (AD) and dementia.
Dementia is a general term of neurodegenerative disease that causes a decline in memory and thinking skills severe enough to reduce a person's ability to perform everyday activities and quality of life.
About 5-8% of all people over the age of 65 have some forms of dementia, and this number doubles every five years above that age.
Most common types of dementia are
* Alzheimer's disease
Alzheimer's destroys brain cells, causing problems with memory, thinking, and behavior severe enough to affect language communication, memory, lifelong hobbies or social life. Alzheimer's gets worse over time, and it is fatal.
Over 1 million people in the US alone are currently afflicted by Alzheimer's disease because of degeneration of hippocampus and cerebral cortex(3) of the brain where memory, language, and cognition are located.
* Absence of acetylcholine
Absence of acetylcholine is a condition caused by damage of nerves located in front of the brain, that lead to language difficulty, memory loss, concentration problem, and reduced mobile skills due to lacking reaction in muscular activity and refection and anxiety- and depression-like behaviors.
3. Dementia due to long-term alcohol abuse
Most classic form of the condition is the Korsakoff's dementia results in extremely poor short term memory often associated with the memory losses of confabulations due to diminished processing resources and/or an encoding or retrieval deficit.
* Dementia associated with Parkinson's disease
Parkinson disease (PD) is a disabling, progressive condition that causes cognitive deficit due to the interruption of frontal-subcortical loops that facilitate cognition and parallel the motor loop, and the loss of substantia nigra pars compacta (SNc) dopamine (DA) neurons.
Besides aging, geographical, hereditary and viral, and toxicological exposure may also correlate to the development of the diseases in the elderly.
Ginger (Zingiber officinale) or ginger root, the second superfood used for thousands of years by mankind, is the genus Zingiber, belonging to the family Zingiberaceae, native to Tamil.
The root has been used in traditional and Chinese medicine for the treatment of dyspepsia, gastroparesis, constipation, edema, difficult urination, colic, etc.
In the course of continued finding a natural ingredient for the treatment of age-related neurological disorders (ANDs), researchers examined the effects of ginger used in traditional medicine for the treatment of various disease symptoms.
Cranberry is an evergreen dwarf shrub, genus Vaccinium, belongings to the family Ericaceae, native to Northern America and Southern Asia. Because of its health benefits, cranberry has been cultivated in some parts of the world for commercial profit and used in traditional and herbal medicine to treat wounds, urinary disorders, diarrhea, diabetes, stomach ailments, and liver problems.
On finding a potential compound for the treatment of neurodegenerative diseases, researchers examined the effect of purified cranberry proanthocyanidins (PAC-1A) on neuroblastoma (NB) cell lines.
On SMS-KCNR cells, PAC-1A caused a loss of proton motive force associated with the increase of generation of reactive oxygen species (ROS) that induce cytotoxicity in the tested cell line.
Furthermore, PAC-1A inhibited neuroblastoma (NB) cells proliferation by reducing the expression of the proteins associated with pro-survivals (Bcl-2, MCL-1, Bcl-xL) and increased levels of proteins associated with pro-apoptosis (Bax, Bad, Bid).
Moreover, pathways involved in apoptosis were also increased by the injection of PAC-1A compared to the inhibition of the expression of pathways involved in the promotion of cell cycle division.
More importantly, cyclophosphamide (CP), the chemo drug used to suppress the immune system function also exhibited by the injection of PAC-1A.
In other words, PAC-1A and CP worked synergistically to increase cytotoxicity and expression of pro-apoptotic markers, reduce cellular antioxidants enzymes (glutathione (GSH) and superoxide dismutase (SOD)) levels.
Additional analysis of the anti-cancer activity of PAC-1A, researchers found that Additional features of PAC-1A also slow down the cancer cell cycle progression and induce cell death via TNF-family death receptor activity.
Based on the findings, researchers said, "PAC-1A has demonstrated the chemotherapeutic potential to treat a broad spectrum of NBs including highly malignant tumors that show resistance to standard chemotherapeutics and apoptotic stimuli".
Taken altogether, cranberry may be considered a remedy for the prevention and treatment of neurodegenerative disease, pending the confirmation of the larger sample size and multicenter human study.
Natural Medicine for Fatty Liver And Obesity Reversal - The Revolutionary Findings To Achieve Optimal Health And Lose Weight
How To Get Rid Of Eye Floaters
Contrary To Professionals Prediction, Floaters Can Be Cured Naturally
Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How-To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months
Back to Kyle J. Norton Homepage http://kylejnorton.blogspot.ca
Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published online, including worldwide health, ezine articles, article base, health blogs, self-growth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bioscience, ISSN 0975-6299.
Sources
(1) Purified cranberry proanthocyanidines (PAC-1A) cause pro-apoptotic signaling, ROS generation, cyclophosphamide retention and cytotoxicity in high-risk neuroblastoma cells by Singh AP1, Lange TS, Kim KK, Brard L, Horan T, Moore RG, Vorsa N, Singh RK. (PubMed)
(1) Regulation of redox status in neuronal SH-SY5Y cells by blueberry (Vacciniummyrtillus L.) juice, cranberry (Vaccinium macrocarpon A.) juice and cyanidin by Cásedas G1, González-Burgos E2, Smith C3, López V4, Gómez-Serranillos MP. (PubMed)
(2) Most common diseases of 50 plus - Diseases of Central Nervous system - Dementia: The Types by Kyle J. Norton
Tuesday, December 7, 2021
Cranberry Protects the Integrity of Bladder Cells Against Bladder Cancer
The bladder formed part of the secretory system is a muscular sac in the pelvis, just above and behind the pubic bone.
The bladder has 2 main functions that store the urine made in the kidneys and control urinary secretion.
Cancer is a group of chronic diseases characterized by cell growth disorderly that starts on the surface of the inner lining tissue of a specific tissue of a gland or organ.
Bladder cancer is the most common type of cancer that affects men twice as frequently as it affects women, Bladder cancer usually starts from the cells on the surface of inner tissue that the lines the bladder.
Bladder cancer depending on the origination of cancer beginning can be classified into
* Transitional cell carcinoma
In the early stage of bladder cancer, normal cells become cancerous in the innermost tissue layer of the bladder which can change shape and stretch without breaking apart. In other words, cancer in this stage is able to stretch when the bladder is full and shrink when the bladder is emptied.
More than 90 percent of bladder cancers begin in the transitional cells
* Squamous cell carcinoma
Cancer begins in squamous cells found in the tissues of the surface of the bladder, due to long-term infection or irritation. About 8 percent of people with bladder cancers begin squamous cells.
* Adenocarcinoma
Cancer originates from the glandular tissue of the bladder, including the surface layer of skin, glands, and a variety of other tissue, due to long-term irritation and inflammation. Only 2 percent of people with the condition have a third bladder cancer type.
The exact causes of bladder cancer are unidentified. However, smoking has been associated with a significant factor that causes the onset of the disease.
Dr. Neal D Freedman, the lead scientist wrote, "Previous studies indicate that the population attributable risk of bladder cancer for tobacco smoking is 50–65% in men and 20–30% in women and that current cigarette smoking triples bladder cancer risk relative to never smoking".
And, "Over the last 30 years, incidence rates have remained stable in the United States (men: 123.8/100,000 person-years to 142.2/100,000 person-years; women: 32.5/100,000 person-years to 33.2/100,000 person-years)".
Cranberry is an evergreen dwarf shrub, genus Vaccinium, belongings to the family Ericaceae, native to Northern America and Southern Asia. Because of its health benefits, cranberry has been cultivated in some parts of the world for commercial profit and used in traditional and herbal medicine to treat wounds, urinary disorders, diarrhea, diabetes, stomach ailments, and liver problems.
On finding a potential compound for the treatment of bladder cancer, researchers examined the anti-proliferative activities of cranberry-derived flavonoids on human bladder tumor cell lines (RT4, SCABER, and SW-780) and non-tumorigenic immortalized human uroepithelial cells (SV-HUC).
According to the tested analysis,
* Quercetin 3-O-glucoside, isorhamnetin (3'-O-methyl quercetin), myricetin and quercetin found in cranberry showed strong concentration-dependent cell growth inhibitory activities in bladder cancer cells with IC50 values in a range of 8-92 μM compared to others.
* Isorhamnetin and myricetin had very low inhibitory activity against SV-HUC even at very high concentrations (>200 μM) compared to bladder cancer cells.
These results strongly suggested that isorhamnetin and myricetin inhibited bladder cancer cells without causing harm to the nearby healthy cells.
Furthermore, according to the results of SW-780 cells incubated with the aforementioned compounds, hyperoside, a member of 3-O-galactoside of quercetin undergoes relatively less metabolic biotransformation (methylation, glucuronidation and quinone formation) compared to quercetin 3-O-glucoside.
Based on the findings, researchers said, "isorhamnetin and quercetin 3-O-glucoside may be the active forms of quercetin in the prevention of bladder cancer".
Taken altogether, cranberry processed abundantly bioactive compounds may be considered a remedy for the prevention and treatment of bladder cancer pending to the confirmation of the larger sample size and multicenter human study.
Natural Medicine for Fatty Liver And Obesity Reversal - The Revolutionary Findings To Achieve Optimal Health And Lose Weight
How To Get Rid Of Eye Floaters
Contrary To Professionals Prediction, Floaters Can Be Cured Naturally
Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How-To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months
Back to Kyle J. Norton Homepage http://kylejnorton.blogspot.ca
Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published online, including worldwide health, ezine articles, article base, health blogs, self-growth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bioscience, ISSN 0975-6299.
Sources
(1) Metabolism and growth inhibitory activity of cranberry derived flavonoids in bladder cancer cells by Prasain JK1, Rajbhandari R1, Keeton AB2, Piazza GA2, Barnes S. (PubMed)
(2) Cranberries and Cancer: An Update of Preclinical Studies Evaluating the CancerInhibitory Potential of Cranberry and Cranberry Derived Constituents by Weh KM1, Clarke J2,3,4, Kresty LA. (PubMed)
(3) Association between smoking and risk of bladder cancer among men and women by Neal D Freedman, PhD, MPH,1 Debra T Silverman, ScD, ScM,1 Albert R Hollenbeck, PhD,2Arthur Schatzkin, MD, DrPH,1 and Christian C Abnet, PhD, MPH. (PMC)
The bladder has 2 main functions that store the urine made in the kidneys and control urinary secretion.
Cancer is a group of chronic diseases characterized by cell growth disorderly that starts on the surface of the inner lining tissue of a specific tissue of a gland or organ.
Bladder cancer is the most common type of cancer that affects men twice as frequently as it affects women, Bladder cancer usually starts from the cells on the surface of inner tissue that the lines the bladder.
Bladder cancer depending on the origination of cancer beginning can be classified into
* Transitional cell carcinoma
In the early stage of bladder cancer, normal cells become cancerous in the innermost tissue layer of the bladder which can change shape and stretch without breaking apart. In other words, cancer in this stage is able to stretch when the bladder is full and shrink when the bladder is emptied.
More than 90 percent of bladder cancers begin in the transitional cells
* Squamous cell carcinoma
Cancer begins in squamous cells found in the tissues of the surface of the bladder, due to long-term infection or irritation. About 8 percent of people with bladder cancers begin squamous cells.
* Adenocarcinoma
Cancer originates from the glandular tissue of the bladder, including the surface layer of skin, glands, and a variety of other tissue, due to long-term irritation and inflammation. Only 2 percent of people with the condition have a third bladder cancer type.
The exact causes of bladder cancer are unidentified. However, smoking has been associated with a significant factor that causes the onset of the disease.
Dr. Neal D Freedman, the lead scientist wrote, "Previous studies indicate that the population attributable risk of bladder cancer for tobacco smoking is 50–65% in men and 20–30% in women and that current cigarette smoking triples bladder cancer risk relative to never smoking".
And, "Over the last 30 years, incidence rates have remained stable in the United States (men: 123.8/100,000 person-years to 142.2/100,000 person-years; women: 32.5/100,000 person-years to 33.2/100,000 person-years)".
Cranberry is an evergreen dwarf shrub, genus Vaccinium, belongings to the family Ericaceae, native to Northern America and Southern Asia. Because of its health benefits, cranberry has been cultivated in some parts of the world for commercial profit and used in traditional and herbal medicine to treat wounds, urinary disorders, diarrhea, diabetes, stomach ailments, and liver problems.
On finding a potential compound for the treatment of bladder cancer, researchers examined the anti-proliferative activities of cranberry-derived flavonoids on human bladder tumor cell lines (RT4, SCABER, and SW-780) and non-tumorigenic immortalized human uroepithelial cells (SV-HUC).
According to the tested analysis,
* Quercetin 3-O-glucoside, isorhamnetin (3'-O-methyl quercetin), myricetin and quercetin found in cranberry showed strong concentration-dependent cell growth inhibitory activities in bladder cancer cells with IC50 values in a range of 8-92 μM compared to others.
* Isorhamnetin and myricetin had very low inhibitory activity against SV-HUC even at very high concentrations (>200 μM) compared to bladder cancer cells.
These results strongly suggested that isorhamnetin and myricetin inhibited bladder cancer cells without causing harm to the nearby healthy cells.
Furthermore, according to the results of SW-780 cells incubated with the aforementioned compounds, hyperoside, a member of 3-O-galactoside of quercetin undergoes relatively less metabolic biotransformation (methylation, glucuronidation and quinone formation) compared to quercetin 3-O-glucoside.
Based on the findings, researchers said, "isorhamnetin and quercetin 3-O-glucoside may be the active forms of quercetin in the prevention of bladder cancer".
Taken altogether, cranberry processed abundantly bioactive compounds may be considered a remedy for the prevention and treatment of bladder cancer pending to the confirmation of the larger sample size and multicenter human study.
Natural Medicine for Fatty Liver And Obesity Reversal - The Revolutionary Findings To Achieve Optimal Health And Lose Weight
How To Get Rid Of Eye Floaters
Contrary To Professionals Prediction, Floaters Can Be Cured Naturally
Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How-To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months
Back to Kyle J. Norton Homepage http://kylejnorton.blogspot.ca
Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published online, including worldwide health, ezine articles, article base, health blogs, self-growth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bioscience, ISSN 0975-6299.
Sources
(1) Metabolism and growth inhibitory activity of cranberry derived flavonoids in bladder cancer cells by Prasain JK1, Rajbhandari R1, Keeton AB2, Piazza GA2, Barnes S. (PubMed)
(2) Cranberries and Cancer: An Update of Preclinical Studies Evaluating the CancerInhibitory Potential of Cranberry and Cranberry Derived Constituents by Weh KM1, Clarke J2,3,4, Kresty LA. (PubMed)
(3) Association between smoking and risk of bladder cancer among men and women by Neal D Freedman, PhD, MPH,1 Debra T Silverman, ScD, ScM,1 Albert R Hollenbeck, PhD,2Arthur Schatzkin, MD, DrPH,1 and Christian C Abnet, PhD, MPH. (PMC)
Sunday, November 28, 2021
Ginger inhibits the Onset and Progression of Arthritis
Scientists may have found a whole food that processes a significant effect in reducing and treatment of arthritis with no side effects, some studies found.
Arthritis is a class of inflammatory diseases that affect the joints.
The most common symptoms of arthritis are joint pain and stiffness.
However, some patients with arthritis may also experience symptoms of redness, warmth, swelling, and decreased the range of motion of the affected joints.
The most common causes of arthritis are the improper healthy of the joint injury in the younger age and infections that affect the integrity of the cartilage.
RA, an autoimmune disorder is a type of arthritis caused by the immune system mistakenly attacking the joint tissues of the body.
The prevalent risk factors associated with the onset of the disease include the increase in age, family history, gender, ethnicity, and obesity.
Some researchers suggested that people who follow the Western diet with high saturated and trans fat, red meat and processed foods, and fewer fruits and vegetables and whole grains are also at an increased risk of arthritis.
According to the study published in the journal JCI Insight on April 19, by the University of Rochester Medical Center in New York, after 3 months of feeding mice a high-fat diet similar to that of a western “cheeseburger and milkshake” regimen, the mice became obese and diabetic and fat percentage was double compared to mice fed with a healthy, low-fat diet.
The contribution of overweight of obesity caused by long-term intake of the Western diet may contribute to the link of obesity in the risk of arthritis.
Ginger (Zingiber officinale) or ginger root, the second superfood used for thousands of years by mankind, is the genus Zingiber, belonging to the family Zingiberaceae, native to Tamil.
The root has been used in traditional and Chinese medicine to treat dyspepsia, gastroparesis, constipation, edema, difficult urination, colic, etc.
With an aim to reconfirm the traditional medicine use of ginger for the treatment of chronic inflammatory diseases, the research team the examine the turmeric (rich in curcuminoids) and ginger (rich in gingerols and shogaols) rhizomes effect in patients with arthritis rat adjuvant-induced arthritis (AIA) both plants at the dose 200 mg/kg body weight were orally administrated.
Turmeric and ginger exerted a significantly suppressed (but with different degrees) the incidence and severity of arthritis by increasing the production of anti-inflammatory and decreasing pro-inflammatory cytokines.
Both turmeric and ginger also restored the antioxidant enzymes in the rats.
In the anti-arthritic activity, turmeric was more effective compared to those of ginger and indomethacin (a non-steroidal anti-inflammatory drug), especially when the treatment started from the day of arthritis induction.
Interestingly, The percentage of disease recovery was 4.6-8.3% and 10.2% more in turmeric compared with ginger and indomethacin, respectively.
Dr. the lead author said, after taking into account co and confounders, "the anti-inflammatory/anti-oxidant activity of turmeric over ginger and indomethacin, which may have beneficial effects against rheumatoid arthritis onset/progression as shown in AIA rat model".
The findings indicated a potential effect of ginger against arthritis although to a lesser extent than those of turmeric.
Furthermore, the investigation of the potential of hydroalcoholic extract of Zingiber officinale rhizomes (Z. officinale extract) in ameliorating inflammatory process in rat collagen-induced arthritis, also found that* Z. officinale extract in doses higher than 50 mg/kg/day intraperitoneally significantly enhanced the immune function against the progression of arthritis.
* Continued administration of the said volume for 26 days can ameliorate the clinical scores, disease incidence, joint temperature and swelling, and cartilage destruction.
* The anti-arthritis effects were associated with reduced production of proinflammatory cytokines and antibodies.
Most importantly, Z. officinale extract at the dose of 200 mg/kg/day was more superior to those of 2 mg/kg/day of indomethacin compared to most of the measured parameters.
Taken altogether, ginger may be used as a functional food for the prevention and combined with primary medicine for the treatment of arthritis
Natural Medicine for Fatty Liver And Obesity Reversal - The Revolutionary Findings To Achieve Optimal Health And Lose Weight
How To Get Rid Of Eye Floaters
Contrary To Professionals Prediction, Floaters Can Be Cured Naturally
Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How-To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months
Back to Kyle J. Norton Homepage http://kylejnorton.blogspot.ca
Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published online, including worldwide health, ezine articles, article base, health blogs, self-growth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bioscience, ISSN 0975-6299.
Sources
(1) Anti-inflammatory and anti-oxidant properties of Curcuma longa (turmeric) versus Zingiber officinale (ginger) rhizomes in rat adjuvant-induced arthritis by Ramadan G1, Al-Kahtani MA, El-Sayed WM. (PubMed)
(2) Evaluation of the effect of hydroalcoholic extract of Zingiber officinale rhizomes in rat collagen-induced arthritis by Fouda AM1, Berika MY. (PubMed)
(3) Western Diet, With Its High-Fat Content, Linked To ArthritisApr 19, 2018 09:00 AM By Sadhana Bharanidharan, (Medical Daily)
Arthritis is a class of inflammatory diseases that affect the joints.
The most common symptoms of arthritis are joint pain and stiffness.
However, some patients with arthritis may also experience symptoms of redness, warmth, swelling, and decreased the range of motion of the affected joints.
The most common causes of arthritis are the improper healthy of the joint injury in the younger age and infections that affect the integrity of the cartilage.
RA, an autoimmune disorder is a type of arthritis caused by the immune system mistakenly attacking the joint tissues of the body.
The prevalent risk factors associated with the onset of the disease include the increase in age, family history, gender, ethnicity, and obesity.
Some researchers suggested that people who follow the Western diet with high saturated and trans fat, red meat and processed foods, and fewer fruits and vegetables and whole grains are also at an increased risk of arthritis.
According to the study published in the journal JCI Insight on April 19, by the University of Rochester Medical Center in New York, after 3 months of feeding mice a high-fat diet similar to that of a western “cheeseburger and milkshake” regimen, the mice became obese and diabetic and fat percentage was double compared to mice fed with a healthy, low-fat diet.
The contribution of overweight of obesity caused by long-term intake of the Western diet may contribute to the link of obesity in the risk of arthritis.
Ginger (Zingiber officinale) or ginger root, the second superfood used for thousands of years by mankind, is the genus Zingiber, belonging to the family Zingiberaceae, native to Tamil.
The root has been used in traditional and Chinese medicine to treat dyspepsia, gastroparesis, constipation, edema, difficult urination, colic, etc.
With an aim to reconfirm the traditional medicine use of ginger for the treatment of chronic inflammatory diseases, the research team the examine the turmeric (rich in curcuminoids) and ginger (rich in gingerols and shogaols) rhizomes effect in patients with arthritis rat adjuvant-induced arthritis (AIA) both plants at the dose 200 mg/kg body weight were orally administrated.
Turmeric and ginger exerted a significantly suppressed (but with different degrees) the incidence and severity of arthritis by increasing the production of anti-inflammatory and decreasing pro-inflammatory cytokines.
Both turmeric and ginger also restored the antioxidant enzymes in the rats.
In the anti-arthritic activity, turmeric was more effective compared to those of ginger and indomethacin (a non-steroidal anti-inflammatory drug), especially when the treatment started from the day of arthritis induction.
Interestingly, The percentage of disease recovery was 4.6-8.3% and 10.2% more in turmeric compared with ginger and indomethacin, respectively.
Dr. the lead author said, after taking into account co and confounders, "the anti-inflammatory/anti-oxidant activity of turmeric over ginger and indomethacin, which may have beneficial effects against rheumatoid arthritis onset/progression as shown in AIA rat model".
The findings indicated a potential effect of ginger against arthritis although to a lesser extent than those of turmeric.
Furthermore, the investigation of the potential of hydroalcoholic extract of Zingiber officinale rhizomes (Z. officinale extract) in ameliorating inflammatory process in rat collagen-induced arthritis, also found that* Z. officinale extract in doses higher than 50 mg/kg/day intraperitoneally significantly enhanced the immune function against the progression of arthritis.
* Continued administration of the said volume for 26 days can ameliorate the clinical scores, disease incidence, joint temperature and swelling, and cartilage destruction.
* The anti-arthritis effects were associated with reduced production of proinflammatory cytokines and antibodies.
Most importantly, Z. officinale extract at the dose of 200 mg/kg/day was more superior to those of 2 mg/kg/day of indomethacin compared to most of the measured parameters.
Taken altogether, ginger may be used as a functional food for the prevention and combined with primary medicine for the treatment of arthritis
Natural Medicine for Fatty Liver And Obesity Reversal - The Revolutionary Findings To Achieve Optimal Health And Lose Weight
How To Get Rid Of Eye Floaters
Contrary To Professionals Prediction, Floaters Can Be Cured Naturally
Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How-To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months
Back to Kyle J. Norton Homepage http://kylejnorton.blogspot.ca
Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published online, including worldwide health, ezine articles, article base, health blogs, self-growth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bioscience, ISSN 0975-6299.
Sources
(1) Anti-inflammatory and anti-oxidant properties of Curcuma longa (turmeric) versus Zingiber officinale (ginger) rhizomes in rat adjuvant-induced arthritis by Ramadan G1, Al-Kahtani MA, El-Sayed WM. (PubMed)
(2) Evaluation of the effect of hydroalcoholic extract of Zingiber officinale rhizomes in rat collagen-induced arthritis by Fouda AM1, Berika MY. (PubMed)
(3) Western Diet, With Its High-Fat Content, Linked To ArthritisApr 19, 2018 09:00 AM By Sadhana Bharanidharan, (Medical Daily)
Thursday, November 18, 2021
Herbal Angelica, the Antioxidant Herbal Remedy
Antioxidants are stable atoms produced either by the host body or intake of dietary antioxidants rich food with the function that inhibits oxidation caused by free radicals.
Free radicals are highly reactive molecules with an unpaired electron on the outer ring of the atom.
Due to its nature to become stable, free radicals readily to donate or steal an electron from other molecules, leading to the chain of domino's effect that can not be stopped until either the electrons are paired or inhibited by antioxidants.
This chain of reaction is the cause of oxidative stress, a condition is associated with either overexpression of free radicals or depletion of antioxidant enzymes produced by the host organs.
Overexpression of free radicals is known to cause damage in contributing to the etiology of many chronic health problems such as cardiovascular and inflammatory disease, cataracts, and cancer by inducing the alternation of lipids, proteins, and cell DNA damage.
Colon cancer is relatively very common and slowly growing and progressing in a predictable way.
Most cases of primary colon cancer start in the cell on the surface of the inner lining of the colon. At the early stage. most patients with colon cancer do not experience any symptoms.
However, at the advanced stage, the tumor not only can spread to other healthy tissue and organs a distance away through blood and fluid circulation but also suppress the nearby tissue and nerve cells.
The progression of colon cancer at this stage not only induces symptoms of the change in bowel habits, the change in the consistency of your stool, that lasts longer than four weeks but also causes rectal bleeding and persistent abdominal severe pain.
According to the statistic by the American Cancer Society, in the US, there are
97,220 new cases of colon cancer were diagnosed in 2018. The lifetime risk of developing colorectal cancer is 1 in 22 (4.49%) for men and 1 in 24 (4.15%) for women.
Angelica or Dang Qui is a herb of Genus Angelica from the family Apiaceae, indigenous to China.
The herb has been used as a Queen herb in traditional Chinese medicine antispasmodic and vasodilatory agent, and to balance the hormones in women for a normal menstrual cycle and menstruation and strengthen heart, spleen, kidneys, and liver for both men and women, etc. In other words, it is used to treat gynecological ailments, fatigue, mild anemia, and high blood pressure. It has analgesic, anti-inflammatory, etc.
On finding a potential compound for the prevention and treatment of diseases associated with oxidative stress, researchers examined the antioxidant activity of Angelica dahurica extract in the HT-29 colon cancer cell line.
According to the A HPLC-DAD analysis, the antioxidant anti-cancer activity of the extract was attributed to the phytochemicals Imperatorin and isoimperatorin, the major coumarins in the ethanol-ethyl acetate active fraction.
In other words, Angelica dahurica extract exerted the antioxidant cancer effect by activating the pro-apoptotic proteins caspase cascade and cell cycle arrest and inhibiting the proteins associated with anti-apoptotic expressions
Based on the results, researchers said, "the ant-cancer activity of the organic extract of Angelica dahurica Radix against colon cancer cells".
Taken altogether, Herbal Angelica consists of the ethanol-ethyl acetate active fraction may be considered a functional herbal medicine for improving antioxidant activity against colon cancer, pending to larger sample size and multicenter human study.
Natural Medicine for Fatty Liver And Obesity Reversal - The Revolutionary Findings To Achieve Optimal Health And Lose Weight
How To Get Rid Of Eye Floaters
Contrary To Professionals Prediction, Floaters Can Be Cured Naturally
Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You. How-To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months
Back to Kyle J. Norton Homepage http://kylejnorton.blogspot.ca
Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published online, including worldwide health, ezine articles, article base, health blogs, self-growth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bioscience, ISSN 0975-6299.
Sources
(1) Anti-oxidant and anti-cancer activities of Angelica dahurica extract via induction of apoptosis in colon cancer cells by Zheng YM1, Shen JZ2, Wang Y2, Lu AX2, Ho WS. (PubMed)
Antimigraine
(1) Chemical Composition and Antimigraine Activity of Essential Oil of Angelicae dahuricae Radix. by Sun J1, Li H2, Sun J2, Liu H3, Chen J2, Wang C. (PubMed)
Free radicals are highly reactive molecules with an unpaired electron on the outer ring of the atom.
Due to its nature to become stable, free radicals readily to donate or steal an electron from other molecules, leading to the chain of domino's effect that can not be stopped until either the electrons are paired or inhibited by antioxidants.
This chain of reaction is the cause of oxidative stress, a condition is associated with either overexpression of free radicals or depletion of antioxidant enzymes produced by the host organs.
Overexpression of free radicals is known to cause damage in contributing to the etiology of many chronic health problems such as cardiovascular and inflammatory disease, cataracts, and cancer by inducing the alternation of lipids, proteins, and cell DNA damage.
Colon cancer is relatively very common and slowly growing and progressing in a predictable way.
Most cases of primary colon cancer start in the cell on the surface of the inner lining of the colon. At the early stage. most patients with colon cancer do not experience any symptoms.
However, at the advanced stage, the tumor not only can spread to other healthy tissue and organs a distance away through blood and fluid circulation but also suppress the nearby tissue and nerve cells.
The progression of colon cancer at this stage not only induces symptoms of the change in bowel habits, the change in the consistency of your stool, that lasts longer than four weeks but also causes rectal bleeding and persistent abdominal severe pain.
According to the statistic by the American Cancer Society, in the US, there are
97,220 new cases of colon cancer were diagnosed in 2018. The lifetime risk of developing colorectal cancer is 1 in 22 (4.49%) for men and 1 in 24 (4.15%) for women.
Angelica or Dang Qui is a herb of Genus Angelica from the family Apiaceae, indigenous to China.
The herb has been used as a Queen herb in traditional Chinese medicine antispasmodic and vasodilatory agent, and to balance the hormones in women for a normal menstrual cycle and menstruation and strengthen heart, spleen, kidneys, and liver for both men and women, etc. In other words, it is used to treat gynecological ailments, fatigue, mild anemia, and high blood pressure. It has analgesic, anti-inflammatory, etc.
On finding a potential compound for the prevention and treatment of diseases associated with oxidative stress, researchers examined the antioxidant activity of Angelica dahurica extract in the HT-29 colon cancer cell line.
According to the A HPLC-DAD analysis, the antioxidant anti-cancer activity of the extract was attributed to the phytochemicals Imperatorin and isoimperatorin, the major coumarins in the ethanol-ethyl acetate active fraction.
In other words, Angelica dahurica extract exerted the antioxidant cancer effect by activating the pro-apoptotic proteins caspase cascade and cell cycle arrest and inhibiting the proteins associated with anti-apoptotic expressions
Based on the results, researchers said, "the ant-cancer activity of the organic extract of Angelica dahurica Radix against colon cancer cells".
Taken altogether, Herbal Angelica consists of the ethanol-ethyl acetate active fraction may be considered a functional herbal medicine for improving antioxidant activity against colon cancer, pending to larger sample size and multicenter human study.
Natural Medicine for Fatty Liver And Obesity Reversal - The Revolutionary Findings To Achieve Optimal Health And Lose Weight
How To Get Rid Of Eye Floaters
Contrary To Professionals Prediction, Floaters Can Be Cured Naturally
Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You. How-To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months
Back to Kyle J. Norton Homepage http://kylejnorton.blogspot.ca
Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published online, including worldwide health, ezine articles, article base, health blogs, self-growth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bioscience, ISSN 0975-6299.
Sources
(1) Anti-oxidant and anti-cancer activities of Angelica dahurica extract via induction of apoptosis in colon cancer cells by Zheng YM1, Shen JZ2, Wang Y2, Lu AX2, Ho WS. (PubMed)
Antimigraine
(1) Chemical Composition and Antimigraine Activity of Essential Oil of Angelicae dahuricae Radix. by Sun J1, Li H2, Sun J2, Liu H3, Chen J2, Wang C. (PubMed)
Saturday, November 13, 2021
Cranberry Arrests Breast Cancer Cells in Vitro
The women's breasts are made of tissues that produce milk (glandular tissue) and fat. The size of a woman's breast is totally depending on the amount of fat in the breast.
Cancer is a class of medical condition associated with cell growth uncontrollably in the specific tissue of the gland and organ.
Breast cancer is a medical condition caused by cell growth irregularly due to the alternation of cell DNA that often begins in the cells on the surface of the inner lining of the tissues of the breast either from the inner lining of milk ducts (Ductal carcinoma) or the lobules (Lobular carcinoma) that supply the ducts with milk.
At the advanced stage after colonizing the deeper layer of tissues to form a tumor through proliferation, invasive cancer cells can travel a distance away to infect other healthy tissues and organs, leading to secondary metastasis.
The most common secondary cancers spread by primary breast cancer are bone, liver, lung, and brain cancer.
According to the statistics, in the US, approximately 268,600 new cases of invasive breast cancer will be diagnosed in 2019, along with 62,930 new cases of non-invasive (in situ) breast cancer.
The lifetime risk of getting invasive breast cancer in the North America of a woman is 1/8.
The 5 years survival rate of breast cancer diagnosed in the localized stage is 100%.
The exact causes of breast cancer are not identified. Epidemiologically, aging, genetic proposition, female gender, family history, history of pregnancy, dense breast tissue, and smoking are some of the most prevalent factors that are found in patients with the disease.
However, some researchers the investigated the risk of breast cancer in obese patients suggested that the promotion of a high-fat diet that causes the increased incidences of obesity in the US may have a strongly negative impact to induce the onset of breast cancer in women.
Dr. Manuel Picon‐Ruiz, the lead scientist wrote, "Recent decades have seen an unprecedented rise in obesity, and the health impact thereof is increasingly evident. In 2014, worldwide, more than 1.9 billion adults were overweight (body mass index [BMI], 25‐29.9 kg/m2), and of these, over 600 million were obese (BMI ≥30 kg/m2)".
And, "Obesity is associated both with a higher risk of developing breast cancer, particularly in postmenopausal women and with worse disease outcome for women of all ages".
Cranberry is an evergreen dwarf shrub, genus Vaccinium, belongings to the family Ericaceae, native to Northern America and Southern Asia. Because of its health benefits, cranberry has been cultivated in some parts of the world for commercial profit and used in traditional and herbal medicine to treat wounds, urinary disorders, diarrhea, diabetes, stomach ailments, and liver problems.
On finding a potential compound for the treatment of cancer, researchers examined the effect of the efficacy of cranberry phytochemical extracts significantly inhibited human breast cancer MCF-7 cells.
According to the tested differentiation, at doses of 5 to 30mg/mL, cranberry phytochemical extracts induced apoptosis in MCF-7 cells in a dose-dependent manner, after exposure for 4h.
Compared to the control group, cranberry phytochemical extracts at a dose of 50mg/mL exhibited an additional 25% higher ratio of apoptotic cells to total cells.
Furthermore, at doses from 10 to 50mg/mL cranberry phytochemical extracts exerted significantly arrested MCF-7 cells at G0/G1 phase.
Moreover, A constant increasing pattern of the G1/S index was observed in the cranberry extract treatment group compared to the decrease of G1/S ratio of the control group between 10 and 24h treatment.
Additionally, according to the cell cycle division analysis, cranberry extracts induced cell cycle arrest in the G1/S in MCF-7 cells was approximately 6 times higher than that of the control group.
Based on the findings, researchers after taking other factors into account said," These results suggest that cranberry phytochemical extracts possess the ability to suppress the proliferation of human breast cancer MCF-7 cells, and this suppression is at least partly attributed to both the initiation of apoptosis and the G1 phase arrest".
Taken altogether, cranberry may be considered a remedy for the prevention and treatment of breast cancer, pending the confirmation of the larger sample size and multicenter human study.
Natural Medicine for Fatty Liver And Obesity Reversal - The Revolutionary Findings To Achieve Optimal Health And Lose Weight
How To Get Rid Of Eye Floaters
Contrary To Professionals Prediction, Floaters Can Be Cured Naturally
Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How-To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months
Back to Kyle J. Norton Homepage http://kylejnorton.blogspot.ca
Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published online, including worldwide health, ezine articles, article base, health blogs, self-growth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bioscience, ISSN 0975-6299.
Sources
(1) Cranberry phytochemical extracts induce cell cycle arrest and apoptosis in human MCF-7 breast cancer cells by Sun J1, Hai Liu R. (PubMed)
(2) Obesity and adverse breast cancer risk and outcome: Mechanistic insights and strategies for intervention by Manuel Picon‐Ruiz, PhD, 1 Cynthia Morata‐Tarifa, PhD, 2 Janeiro J. Valle‐Goffin, MD, 3Eitan R. Friedman, MD, 4 and Joyce M. Slingerland, MD, PhD. (PMC)
Cancer is a class of medical condition associated with cell growth uncontrollably in the specific tissue of the gland and organ.
Breast cancer is a medical condition caused by cell growth irregularly due to the alternation of cell DNA that often begins in the cells on the surface of the inner lining of the tissues of the breast either from the inner lining of milk ducts (Ductal carcinoma) or the lobules (Lobular carcinoma) that supply the ducts with milk.
At the advanced stage after colonizing the deeper layer of tissues to form a tumor through proliferation, invasive cancer cells can travel a distance away to infect other healthy tissues and organs, leading to secondary metastasis.
The most common secondary cancers spread by primary breast cancer are bone, liver, lung, and brain cancer.
According to the statistics, in the US, approximately 268,600 new cases of invasive breast cancer will be diagnosed in 2019, along with 62,930 new cases of non-invasive (in situ) breast cancer.
The lifetime risk of getting invasive breast cancer in the North America of a woman is 1/8.
The 5 years survival rate of breast cancer diagnosed in the localized stage is 100%.
The exact causes of breast cancer are not identified. Epidemiologically, aging, genetic proposition, female gender, family history, history of pregnancy, dense breast tissue, and smoking are some of the most prevalent factors that are found in patients with the disease.
However, some researchers the investigated the risk of breast cancer in obese patients suggested that the promotion of a high-fat diet that causes the increased incidences of obesity in the US may have a strongly negative impact to induce the onset of breast cancer in women.
Dr. Manuel Picon‐Ruiz, the lead scientist wrote, "Recent decades have seen an unprecedented rise in obesity, and the health impact thereof is increasingly evident. In 2014, worldwide, more than 1.9 billion adults were overweight (body mass index [BMI], 25‐29.9 kg/m2), and of these, over 600 million were obese (BMI ≥30 kg/m2)".
And, "Obesity is associated both with a higher risk of developing breast cancer, particularly in postmenopausal women and with worse disease outcome for women of all ages".
Cranberry is an evergreen dwarf shrub, genus Vaccinium, belongings to the family Ericaceae, native to Northern America and Southern Asia. Because of its health benefits, cranberry has been cultivated in some parts of the world for commercial profit and used in traditional and herbal medicine to treat wounds, urinary disorders, diarrhea, diabetes, stomach ailments, and liver problems.
On finding a potential compound for the treatment of cancer, researchers examined the effect of the efficacy of cranberry phytochemical extracts significantly inhibited human breast cancer MCF-7 cells.
According to the tested differentiation, at doses of 5 to 30mg/mL, cranberry phytochemical extracts induced apoptosis in MCF-7 cells in a dose-dependent manner, after exposure for 4h.
Compared to the control group, cranberry phytochemical extracts at a dose of 50mg/mL exhibited an additional 25% higher ratio of apoptotic cells to total cells.
Furthermore, at doses from 10 to 50mg/mL cranberry phytochemical extracts exerted significantly arrested MCF-7 cells at G0/G1 phase.
Moreover, A constant increasing pattern of the G1/S index was observed in the cranberry extract treatment group compared to the decrease of G1/S ratio of the control group between 10 and 24h treatment.
Additionally, according to the cell cycle division analysis, cranberry extracts induced cell cycle arrest in the G1/S in MCF-7 cells was approximately 6 times higher than that of the control group.
Based on the findings, researchers after taking other factors into account said," These results suggest that cranberry phytochemical extracts possess the ability to suppress the proliferation of human breast cancer MCF-7 cells, and this suppression is at least partly attributed to both the initiation of apoptosis and the G1 phase arrest".
Taken altogether, cranberry may be considered a remedy for the prevention and treatment of breast cancer, pending the confirmation of the larger sample size and multicenter human study.
Natural Medicine for Fatty Liver And Obesity Reversal - The Revolutionary Findings To Achieve Optimal Health And Lose Weight
How To Get Rid Of Eye Floaters
Contrary To Professionals Prediction, Floaters Can Be Cured Naturally
Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How-To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months
Back to Kyle J. Norton Homepage http://kylejnorton.blogspot.ca
Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published online, including worldwide health, ezine articles, article base, health blogs, self-growth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bioscience, ISSN 0975-6299.
Sources
(1) Cranberry phytochemical extracts induce cell cycle arrest and apoptosis in human MCF-7 breast cancer cells by Sun J1, Hai Liu R. (PubMed)
(2) Obesity and adverse breast cancer risk and outcome: Mechanistic insights and strategies for intervention by Manuel Picon‐Ruiz, PhD, 1 Cynthia Morata‐Tarifa, PhD, 2 Janeiro J. Valle‐Goffin, MD, 3Eitan R. Friedman, MD, 4 and Joyce M. Slingerland, MD, PhD. (PMC)
Sunday, November 7, 2021
The Science of Tea: Green Tea in Risk of Cancers
Green tea, a precious drink processes numbers of health benefits known to almost everyone in Asia and Western world. However, as yin in nature herbal medicine or food, long term injection of large amounts may obstruct the balance of yin-yang, induced "yin excessive syndrome" or "yang vacuity syndrome" including weaken immunity and painful case of GERD,... according to traditional Chinese medicine's Yin-Yang theory. Adding a slice of ginger will do the trick.
Cancers are a class of chronic medical conditions characterized by abnormal cell growth disorderly and uncontrollably in some specific tissues. At the later stage, the malignant cells have a tendency to spread to other tissue distance away from the originated site.
Epidemiological studies strongly suggested that green tea and its bioactive chemical constituents, particularly, Epigallocatechin-3-gallate (EGCG) may have potential and therapeutic implications in reduced risk of various types of cancer(1-49). However, geographic differences where the tea is growth, types of tea, time of harvest, time of feeding, how the tea is fermented,.....may affect the quality of tea in prevention of tumor onset.
1. Breast Cancer
Breast cancer (malignant breast neoplasm) is a cancer that starts in the tissues of the breast either from the inner lining of milk ducts (Ductal carcinoma) or the lobules (Lobular carcinoma) that supply the ducts with milk. there is also rare cases that breast cancer starts in other areas of the breast.
According to the joint study lead by the Xinyang Normal UniversityHenan, Epigallocatechin-3-gallate (EGCG), a bioactive compound in green tea inhibited risk of breast cancer through many mechanisms involving primarily in cell death and survival(1).
In MDA-MB-231 breast cancer cell line, epigallocatechin gallate isolated from green tea induced apoptosis and inhibited tumorigenesis(2) through expression of multiple signaling pathways in breast cancer cells.
EGCG decreased MDA-MB-231 cell viability and significantly down regulated the expression of β-catenin(2) in regulated the coordination of cell–cell adhesion and gene transcription, according to Western blot analysis as patients with breast cancer is found to associate to high levels of β-catenin in breast cancer tissue than in normal tissue.
Dr. Hong OY, the lead author said, "EGCG inhibits the growth of MDA-MB-231 cells through the inactivation of the β-catenin signaling pathway(2). Based on these promising results, EGCG may be a potential treatment for triple negative breast cancer patients.".
In polychlorinated biphenyls (PCBs) accumulated in human breast cancer tissue induced the growth of estrogen-sensitive tumors, EGCG inhibited the early onset of breast cancer through modifying estrogenic activity against cell proliferation in a dose-dependent manner(3).
At dose of at 25 μM, EGCG also exerted antiproliferative and pro-apoptotic action in activation of ERβ receptor(3) to interact with or inhibit ERα in suppressed breast cancer cell growth.
2. Prostate Cancer
Cancers are a class of chronic medical conditions characterized by abnormal cell growth disorderly and uncontrollably in some specific tissues. At the later stage, the malignant cells have a tendency to spread to other tissue distance away from the originated site.
Epidemiological studies strongly suggested that green tea and its bioactive chemical constituents, particularly, Epigallocatechin-3-gallate (EGCG) may have potential and therapeutic implications in reduced risk of various types of cancer(1-49). However, geographic differences where the tea is growth, types of tea, time of harvest, time of feeding, how the tea is fermented,.....may affect the quality of tea in prevention of tumor onset.
1. Breast Cancer
Breast cancer (malignant breast neoplasm) is a cancer that starts in the tissues of the breast either from the inner lining of milk ducts (Ductal carcinoma) or the lobules (Lobular carcinoma) that supply the ducts with milk. there is also rare cases that breast cancer starts in other areas of the breast.
According to the joint study lead by the Xinyang Normal UniversityHenan, Epigallocatechin-3-gallate (EGCG), a bioactive compound in green tea inhibited risk of breast cancer through many mechanisms involving primarily in cell death and survival(1).
In MDA-MB-231 breast cancer cell line, epigallocatechin gallate isolated from green tea induced apoptosis and inhibited tumorigenesis(2) through expression of multiple signaling pathways in breast cancer cells.
EGCG decreased MDA-MB-231 cell viability and significantly down regulated the expression of β-catenin(2) in regulated the coordination of cell–cell adhesion and gene transcription, according to Western blot analysis as patients with breast cancer is found to associate to high levels of β-catenin in breast cancer tissue than in normal tissue.
Dr. Hong OY, the lead author said, "EGCG inhibits the growth of MDA-MB-231 cells through the inactivation of the β-catenin signaling pathway(2). Based on these promising results, EGCG may be a potential treatment for triple negative breast cancer patients.".
In polychlorinated biphenyls (PCBs) accumulated in human breast cancer tissue induced the growth of estrogen-sensitive tumors, EGCG inhibited the early onset of breast cancer through modifying estrogenic activity against cell proliferation in a dose-dependent manner(3).
At dose of at 25 μM, EGCG also exerted antiproliferative and pro-apoptotic action in activation of ERβ receptor(3) to interact with or inhibit ERα in suppressed breast cancer cell growth.
2. Prostate Cancer
According to the Fu Jen Catholic University, New Taipei City, catechin nanoemulsion preparation showed a highest inhibition of growth of PC-3 tumor cells, with concentration being 15.4 μg/mL and 8.5 μg/mL(4).
The inhibition of prostate cancer cell line is observed in cell cycle arrest by regulated proteins involved cell cycle division(4), namely cyclin A, cyclin B, cyclin-dependent kinase 2, and cyclin-dependent kinase 1 expression and activated cell atopotosis and survival.
Dr. Tsai YJ, the lead author said, "Catechin extract and nanoemulsion could induce apoptosis of PC-3 cells through decrease in B-cell lymphoma 2 (bcl-2) expression and increase in cytochrome c expression( in induction of apoptosis) for activation of caspase-3, caspase-8, and caspase-9 (involved cell death)".
In the recruited 404 PCA cases and 395 controls from the same hospital to investigate whether habitual tea consumption, including green, oolong, black and pu'er tea regular green drinkers have a significantly reduced risk in prostate cancer development(5), scientists found that there are inverse relation of tea drinkers and risk of prostate cancer among the habitual pu'er tea drinkers(6)and lower intake of EGCG(5) was observed among cases (54.4 mg) than the controls (72.5 mg).
The differentiation of 7 observational studies and 3 randomized controlled trials retrieved from Cochrane Library, PubMed, Sciencedirect Online, and hand searching.the database, also revealed an interest correlated incidence of PCa decrease with each cup/day increase of green tea(6)..
According of the study(6), "higher green tea consumption was linearly reduced PCa risk with more than 7 cups/day and green tea catechins were effective for preventing PCa".
3. Osteosarcoma
Osteosarcoma is a medical condition of bone cancer characterized by producing immature bone and occurred mostly in children and young adults between the ages of 10 and 30.
According to the study in investigation of the effects of Epigallocatechin-3-gallate (EGCG), in reduced risk of osteosarcoma expression in compared to miR-126 in the proliferation, invasion, migration, and chemotherapeutics resistance in cancer(7), application of Epigallocatechin-3-gallate (EGCG) exerted a significant effect in suppresseed proliferation of human cell line osteosarcoma MG63 and U2OS cells in a concentration-dependent and time-dependent manner and inhibited cancer cell lines at the concentration of 0.05 g/L on U2OS cells equivalent to 20 μM cisplatin (DDP)(7)
In compared to green tea extract induced cell death by interfering in cell cycle arrest, miR-126, the chemo suppressor drug induced apoptosis and inhibited proliferation in U2OS cell line but without significant effects on phase 1 of cancerous cell cycle division(7).
Researchers suggested application of Epigallocatechin-3-gallate (EGCG) may increase the effect of tumor suppressing drug miR-126 and for treatment of osteosarcoma(7).
The inhibition of miR-126 osteosarcoma cells without inducing apoptosis and cells proliferation in cell cycle division(7) is attributed to the extract in target of sequences in reducing the expression of the targeted genes.
In other words, the extract can bind directly to inhibit DNA transcription and prevented mRNA in transmitting such transcription in initiated cancer development.
Other researchers suggested that the inhibition of Epigallocatechin-3-gallate (EGCG) in reduced cancerous cell death does not limit to the function of cell cycle arrest(8).
The phytochemical compoud also expressed the apoptotic effect through modulating gene expression of cancer cell line and induced degradation of cancerous cellular structure(8).
Additional evaluation of the phytochemical Epigallocatechin-3-gallate (EGCG) and the tumor suppressed drug miR-1 effect in osteosarcoma, researchers also found that Epigallocatechin-3-gallate has a profound and positive effect in improved the efficacy of miR-1 in induced cell apoptosis and proliferation observed in cancer cell lines MG-63 and U-2OS(8).
MG-63 and U-2OS treated by miR-1 and Epigallocatechin-3-gallate (EGCG) decreased c-MET expression, which is an indication of cancers development(8).
The combined application of Epigallocatechin-3-gallate (EGCG) and c-MET inhibitor (crizotinib) also displayed a significant inhibition of MG-63 and U-2OS cancer cell proliferation)8).
In the study of the effects of Se-enriched Ziyang green tea, containing chemical compound mannose, rhamnose and fucose in anti tumor activity on human osteosarcoma U-2 OS cells in vitro and in vivo, researchers found that Se-ZYTP at concentration of 25, 50, 100 and 200 μg/ml exerted a significantly inhibition of proliferation of human osteosarcoma U-2 OS cells in a concentration-dependent fashion(9).
In cancer cell line In U-2 OS cancer induced in BALB/c athymic mice model, Se-ZYTP oral administration at three doses of 100, 200 and 400mg/kg body weight (B.W.) daily for 28 days resulted in tumor regression as compared to model control without causing any serious side effects(9).
The illustration suggested that other chemical compounds found in green tea may also have the potential in suppression of proliferation and induced apoptosis of osteosarcoma.
The anti osteosarcoma activities of Se-enriched Ziyang green tea may be attributed to the stimulation in increased pro-apoptotic protein Bax expression(9)(upregulated by the tumor suppressor(9) protein p53 in induced apoptosis) and decreased expression levels of anti-apoptotic protein Bcl-2(9)(regulator proteins that regulate cell death) and NG2(9)(involved cell survival, migration and angiogenesis), some researchers suggested.
4. Lung Cancer
Lung cancer is a medical condition characterized by cells growth disorderly and uncontrollably of lung tissues.
In the study to investigate the anti lung cancer effect of Epigallocatechin-3-gallate (EGCg), the major polyphenolic compound present in green tea, after taking into account of other con founders, researchers at the joint study lead by the Kyushu University of Health & Welfare, suggested that
the phychemical induces apoptosis of lung cancer through suppression of cell division, in cell culture(10).
In human A549 human non-small-cell lung cancer cell line, EGCg inhibited cancerous cell proliferation by interfering mRNA expression in modulation of apoptotic cell death(10)
Additionally, application of 100 μM EGCg for 24 h. exhibited cancerous morphological changes, thus reducing cell proliferation(10).
The study also revealed that the efficacy of EGCg inhibited B-cell lymphoma-extra large (Bcl-xL)(10) through expression of mRNA and suppression of gene in related to cell death.
Epigallocatechin-3-gallate (EGCg) in inhibited gene expression in risk of lung cancer by binding HIF-1α, in promoted cell proliferation and anchorage-independent growth, researchers launched a study to elucidate the role of microRNA in the EGCG inhibition of tobacco carcinogen-induced lung tumors in A/J mice found that 26 potential targeted genes of the 21 microRNAs. with the mRNA expression profiles may have some implications in increased lung cancer risk(11).
Application of EGCg, indeed, demonstrated a significant effect in improved cell regulation and reduced cell proliferation through many mechanisms, including regulation of AKT pathway(11) in promoted survival and growth in response to extracellular signals and NF-κB expression(11) in cellular responses to stimuli such as stress, cytokines, free radicals, heavy metals, ultraviolet irradiation and MAP kinases(11), involved variety of fundamental cellular processes such as proliferation, differentiation, motility, stress response, apoptosis, and survival.
In other words, Epigallocatechin-3-gallate (EGCg) effect reduced risk and treatment of lung cancer is attributed to the inhibition of expression of RNA in transmitting information to proteins with function to initiated cancer cell change, including cell proliferation and apoptosis.
The findings also suggested that green tea Epigallocatechin-3-gallate (EGCg) has a strong effect in reduced risk lung cancer through both expression of mutate and cancer-related genes(11).
Mutated genes expression has been identified in contribution to cancer development and progression, therefore by target the expression of such genes may help scientists in explore the origins of abnormal gene expression in compared to normal cells.
Other researchers suggested that by targeting both DNA and RNA data to identify alternative expression of mutated gene in patients of lung cancer may open the door by offering specific treatment only for such patients.
More precisely, by identified such gene in cancer cell patients, scientist may prescribe gene targeting technology, specific medication and treatment to stop cancer from growing and spreading.
Further differentiation of the effect of green tea extract in lung cancer risk, researchers at the University in Toruń indicated that green tea extract catechins demonstrated a significant effect in inhibition of lung cancer line A549(12) independent to doses applied and increased cell and marker of cell degradation(12) and green tea extract catechins also expressed a strong protective effect in reduced self cause of toxicity(12)
This illustration indicated that green tea extract catechins exert anti lung cancer progression activity through protection against destruction and damage of redundant cellular components occurring in vacuoles within the cell without induced side effects.
5. Ovarian Cancer
In the analysis of the EGCG effects on 8 ovarian cancer cell lines (SKOV3, CAOV3, OVCAR3, OVCAR10, A2780, CP70, C30, and C200) and showed IC50s for EGCG at the micromolar range, researchers found that EGCG inhibited all ovarian cancer cell lines in dose depending manner(13).
Normal dose application of EGCG displayed a significant increase of antioxidant in reduced ROS over expression(13) of oxidative stress in inhibited ovarian cancer through cell cycle arrest in G2/M phase(13).
Administration of EGCG at common dose not only demonstrated a 6 fold increase of cisplatin potency for treatment of SKOV3, CAOV3, and C200 cells, but also attenuated the chemodrug toxicity(13).
However, the effect of EGCG on the formation of reactive oxygen species (ROS) was biphasic.
The phytochemical was shown to induce and decrease ROS formation in different doses.
Therefore, higher dose of EGCG promoted over expression of antioxidants in reduced oxidative stress may amplify the toxicity in ameliorated human cancer cells proliferation and induced apoptosis.
Dr.Bae KH, the lead author(13) said, "EGCG may accentuate oxidative stress to inhibit growth of ovarian cancer cells and sensitize them to cisplatin".
Other researchers in the study of toxicity of EGCG suggested that green tea catechin, (-)-epigallocatechin-3-O-gallate (EGCG) as a potent adjuvant to enhance the anti tumor efficacy of cisplatin while mitigating its harmful side effects through various mechanisms.
Application of EGCG showed to promote hyaluronic acid function in regulation of normal cell division and prevention of the acid in initiation of cancerous cell proliferation(14).
Hyaluronic acid, a polysaccharide molecule, plays an important role in cell proliferation and migration, and may involve in the progression of some malignant tumors.
Additionally, EGCG also expressed anti cancer effect by promoting the injection of chemo medicine cisplatin into the CD44-over expressing(14) cancer cells to prevent over growth of tumor cells.
In regard to toxicity, EGCG on one hand, reduced capacity of oxidative stress in initiated toxicity against off-target organs and tissues through induction of significant antioxidant activity(14) on the hand, and stimulated function of toxicity originating from cisplatin into the target tumors.
Green tea catechin-based micellar nanocomplexes also inhibited superiorly against tumor growth with no injection of cisplatin(14) and expressed a significant inhibition without induced toxicity in both cancer cells suspended in culture medium and injected into the animal models and peritoneal metastatic model of human ovarian cancer(14).
In other words, green tea catechin-based micellar nanocomplexes may be considered as a safe and effective cisplatin nanomedicine for ovarian cancer treatment..
In the additionally examined the effect of EGCG in suppressing ovarian cancer cell growth in 3 human ovarian cancer cell lines (p53 negative, SKOV-3 cells; mutant type p53, OVCAR-3 cells; and wild type p53, PA-1 cells),
EGCG decreased tumor growth in each cell line in a dose-dependent fashion and induced apoptosis and cell cycle arrest, particular to the G(1) phase in SKOV-3 and OVCAR-3 cells in compared to G(1)/S transition phase arrest in PA-1 cells(15).
The chemical also acted differentiately in upregulated the expression of genes and proteins in promoted cancer cell arrest, suppressed tumor growth and induced cell death(15) (Bax, p21, Retinoblastoma, cyclin D1, CDK4, Bcl-X(L)) by more than 2-fold.
6. Melanoma
Melanoma, is a medical condition characterized by irregular cell growth of pigment-containing cells known as melanocytes.
According to the study, approximately 7,200 Canadians will be diagnosed with melanoma skin cancer.
In the review of literature published online, green tea bioactice EGCG significantly inhibited the growth, migration and invasion of melanoma cells through numbers of mechanism.
Gene implications in initiated cancer development and cancerous cells proliferation have gone through extensive research, particularly in melanoma.
In melanoma, green tea biactice EGCG demonstrated a significant effect in knockdown gene over expression (TRAF6)(16) in reduced migration and invasion of melanoma.
TRAF6 is a protein with function in activation of IkappaB kinase (IKK) in response to inflammation.
Green tea biactive EGCG directly bound to TRAF6 in melanoma in attenuated the interaction of
between TRAF6 and UBC13(E2) in activated the protein(16) (IkappaB kinase (IKK)) in production of pro inflammatory cytokins.
The ubiquitin-conjugating enzyme(UBC13(E2)) are essential in activation protein (NF- kappa B) in controls transcription of DNA, cytokine production and cell survival.
The phytochemicals also suppressed the TRAF6 E3 ubiquitin ligase activity of the tumor generated by TRAF6(16) in regulation of important biological processes, particularly, in cell division and for the survival of the tumors.
Green tea biactice EGCG also regulated the gene expression of proteins (IκBα and p-TAK1 e) in modulated and inactivated NF-κB-directed gene expression(16) of inflammation, immunity, cell proliferation, differentiation, and survival in melanoma.
Dr. Zhang J(16), the lead author said, "EGCG is a novel E3 ubiquitin ligase inhibitor that could be used to target TRAF6 for chemotherapy or the prevention of melanoma".
Other researchers in focus of Green tea polyphenol (-)-epigallocatechin-3-O-gallate (EGCG) effect in attenuated and treatment of melanoma in the gene implication via MicroRNAs (17)(miRNAs, non-coding RNAs involved in various biological processes by regulating their target genes) also indicated that green tea polyphenol (-)-epigallocatechin-3-O-gallate (EGCG) inhibited melanoma tumor growth by activating 67-kDa laminin receptor (67LR) signaling(17) which has an function in down regulated tumor cell proliferation and tumor formation by inducing apoptosis.
The bioactive compound also up-regulated miRNA-let-7b expression in induced tumor suppressor function in decrease function of 67LR in enhanced invasive and metastatic melanoma cells.
Indeed, green tea EGCG-also displayed a significant effect in promote function of let-7b in altering the traits,of malignant cell in melanoma through regulating the expression of HMGA2.with action as DNA transcriptional regulator(17).
Green tea EGCG. also induced expression of let-7b in inhibitions of oncoproteins and activation of tumor suppressor via tumor-over expressed 67LR in activation of PP2A(17), a tumor suppressor. through adenylate cyclase/cAMP pathway in cell communication.
In compared the effects of TNF-related apoptosis-inducing ligand (TRAIL), a protein with function in in induced tumor cells apoptosis. and green tea bioactive EGCG effects in A375 melanoma cell line, researchers found that TRAIL application group demonstrats a strong effect in inhibition with apoptosis rate was 11.8% at dose of 150ng/mL in compared to green tea EGCG treatment group of 5%-7%(18).
In combined TRAIL and green tea EGCG treatment groups, the inhibited rate increased sufficiently to 48.9 - 59.1%(18) and EGCG effective in treatment of melanoma was attributed to activity of caspase-3 rather than caspase-8 in mediation of programmed cell death (apoptosis)(18).
7. Liver Cancer
In liver cancer animal model induced by chronic exposure of N-nitrosodiethylamine (NDEA), a carcinogenic and mutagenic organic compound, application of green tea bioactive compounds Epigallocatechin gallate (EGCG) and Theaflavin (TF) demonstrated a strong effect in reduced initiation of cancer formation(19) and potential chemopreventive effect in pre and post treatment(19) of the injected animal.
EGCG/TF action in restrain the over expression of liver cancer cells proliferation was the result of modulated similarly to those of CD44-specific cell membrane binding combined with near-infrared irradiation in induction of cellular apoptosis(19).
High CD44-positive expression is found to associate to acute cancer cells killing.
The restriction processes of EGCG/TF in modification of onset of liver cancer development, was also found to modify multiple biogenesis involved maintaining a relatively stable equilibrium in organs tissues(self-renewal Wnt/β-catenin, Hh/Gli1 pathways)(19) in gene with implication of cell cycle progression, apoptosis and cellular transformation and cell differentiation and proliferation(Cyclin D1, cMyc and EGFR)(19) and tumor suppressor (E-cadherin)(19) during the carcinogenesis processes.
The therapeutic efficacy of tea polyphenols epigallocatechin gallete (EGCG) and theaflavin (TF) also regulated the proteins expression of cell differentiation, polarity and proliferation(the self-renewal Wnt and Hedgehog (Hh) pathways(20).during CCl4/N-nitosodiethylamine-induced mouse liver carcinogenesis.
Green tea bioactive tea polyphenols epigallocatechin gallete (EGCG) and theaflavin (TF) induced chemo preventive potential in maintain cell integrity at the 30 weeks of CCl4/N-nitosodiethylamine application.
Continuous administration of EGCG/TF exerted a strong impact in reduced proliferation and increased apoptosis(20), as well as decreased function of hepatic progenitor cells (HPCs)(20) in participated restoration of the cancerous liver tissue and population with cancer stem cell-like characteristics in liver carcinoma observed by AFP and CD44 expression(20).in CCl4/N-nitosodiethylamine-induced mouse liver carcinogenesis.
During the restriction processes of EGCG/TF, the bioactive compounds also modulated the expression of tumor progression to a more invasive phenotype(20)(phospho-β-catenin-Y-654), tumor suppressor(β-catenin)(20), the proliferation, migration and invasion of liver cancer gene(sFRP1 )(20) and gene in control tumor suppressor(β-catenin)(20).
In other words, green tea EGCG/TF inhibited the contaminated cells inflicted by injection of CCl4/N-nitosodiethylamine to prevent the initiation of liver cancer through modulation of certain gene expressions involved in liver cancer progression.
In short, the inhibition of liver carcinogenesis by EGCG/TF was attributed to reduction in hepatocyte progenitor cell and stem cell population by restoring liver cancerous cells damage through various mechanisms indicated above.
8. Gastric Cancer
According to medical literature published online, in vascular endothelial growth factor (VEGF) over expression in formation of new blood vessel to provide nutrients and fluids for the survival of gastric cancer, application of green tea (-)-Epigallocatechin-3-gallate (EGCG) restricted the pro-inflammatory cytokine interleukin-6 (IL-6)(21) induced VEGF(21) in stimulated signal protein in transmitted alternated DNA transcript and activated suppression of anti cell apoptosis transcription 3 (Stat3)(21).
Oral administration of green tea extract decreased levels of IL-6, VEGF overexpression in doses depending manner.
In compared to healthy individual, IL-6, VEGF expression were found to increase more than 2.4-fold in patients with gastric cancer(21).
The chemical compound also exhibited anti cancer progressive activity by blocking the process of complex sequence of VEGF expression in transferring faulty DNA transcription to signal proliferation of cancer cells through mRNA in protein synthesis.
In other words, green tea inhibited the progression of cancer development induced by over expression of vascular endothelial growth factor (VEGF) was total depended EGCG's DNA biding activity(21) and inhibition of Stat proteins(21) in differentiated cytoplasm into the nucleus, the important step in initiation of cancer progression.
According to experiments in vitro and vitro, EGCG also expressed a significant effect in the reduced the IL-6 properties in stimulated vascular endothelial cells in promoted cancer cells proliferation and formation.
After taking into account of other con founders, Dr. Zhu BH, the lead author(21) said, "EGCG inhibits IL-6-induced VEGF expression and angiogenesis via suppressing Stat3 activity in gastric cancer, which has provided a novel mechanistic insight into the anti-angiogenic activity of EGCG".
Additionally, researchers in further illustration of the effect of EGCG (0, 5, 10, 25 or 50 μmol/L), in human gastric cancer cells (AGS) caused by IL-6 (50 μg/L) suggested that interleukin 6 (IL-6)over expression not only significantly increased VEGF expression in AGS gastric cancer cells, but also increased function of mRNA expression by more than 2.4 fold(22) in the process to initiated tumor development, in dose depending manner.
Treatment of bioactive EGCG with doses of 0, 5, 10, 25 or 50 μmol/L demonstrated a therapeutic activities in reduced the release protein of VEGF to stimulated and mRNA expression of alternated transcript.
In compared to AG490, a Stat3 pathway inhibitor used for treatment of gastric cancer, green tea EGCG blocked the sequence of transcript transferred step in induced expression of pSTAT3(22) in proliferation of cells and tumor tissues without causing change in STAT3 gene(22).
In 5-FU resistance of GC SGC7901/FU and MGC803/FU, gastric cancer cell lines, injection of epigallocatechin gallate (EGCG) displayed a significantly suppressed the proliferation and tumor growth through reversed the 5-FU(23) resistance of GC cells via inhibited the P-glycoprotein 1 (MDR1)(23) and P-glycoprotein (P-gp)(23) also known as multidrug resistance proteins in transmitted transcript in obstructing cell internalization of chemotherapeutic agents and developing transporter mediated resistance by cancer cells during anti-tumor treatments.
9. Colon Cancer
According to the study by the University College of Medicine, Seoul, application of EGCG on HT-29 colon cancer cells showed a significant effect in inhibition of cell cycle progression of protein in COX-2 expression(24) through activation of AMPK activity(24) in promoted metabolic tumor suppressor by regulating energy levels, enforcing metabolic checkpoints and inhibiting cell growth.
Cyclooxygenase(COX)-2, is an enzyme with function in speeding up the production of hormone prostaglandins in regulated cell proliferation and cell apoptosis.
AMPK(5' AMP-activated protein kinase) plays a role in cellular energy homeostasis, activation of AMPK(24) may result in tumor growth inhibition, cell cycle arrest, and apoptosis of cancer cells in some tumor types/contexts.
In inhibition of COX-2 expression, green tea EGCG reduced prostaglandin E(2) secretion(24), thus reducing risk of the hormone)(24) in modulated angiogenesis, including the process of new blood vessel formation, promoted proliferation, migration and formation of endothelial cells, lining the interior surface of blood vessels and lymphatic vessels.
The study also emphasized that inhibiting AMPK by an AMPK inhibitor may interrupt the function of the bioactive compound in initiated such changes(24).
Continuously, the activation of enzyme AMPK also had a strong implication on VEGF(24) (vascular endothelial growth factor) and glucose transporter in facilitated Glut-1(24) in transport of glucose across the plasma membranes of mammalian cells in EGCG-treated cancer cells.
Application of EGCG activated AMPK enzyme also modulated the production of ROS without causing ROS expression in initiated tumor progression and damage to cellular structures(24), such as the lipid membrane, protein and nucleic acid but inducing cancer cells DNA mutations and compromised genome integrity, subsequently in cancer cells senescence and death.
In other aspect of study of colon cancer in animal model, diminished levels of retinoid X receptor-alpha (RXRα) in regulated cancer cell growth and modulated suppress tumorigenesis may have a profound effect in cell proliferation.
Application of green tea bioactive EGCG expressed a significant effect in restored RXRα protein and expression levels caused by methylation function in alternated the activity of a DNA segment(25) without changing the sequence, thus reducing risk of cancer expansion.
Additional differentiation also suggested that EGCG induced methylation changes in several other colon cancer related genes to restore the levels of RXRα without causing a decrease in global methylation(25) in maintaining the epigenetic state of individual genes.
Change of globe methylation expression is found to associate to the occurrence of cancer.
Retinoid X receptor-alpha (RXRα) is a nuclear receptor with function in regulated cancer proliferation and modulated suppression of tumorigenesis.
10. Lymphoma
In EL4 cancer cells line, injection of green bioactive saponin stimulated the immunomodulatory activity in inhibited EL4 cells line through regulated cytokine expression induced by inflammation and mitogen-activated protein kinases (MAPK) signaling pathway(26) involved in a variety of fundamental cellular processes such as proliferation, differentiation, motility, stress response, apoptosis, and survival.
Furthermore, injected saponin also reduced the expression of EL4 cells line in tumor proliferation by interrupting the process of sequence of mutated DNA transcript in mRNA expression in transmitting transcript by initiating production of inflammatory cytokines to reverse transcription polymerase chain reaction in making copies of alternated gene(26), thus attenuating risk of tumor growth, tumor progression and immuno-suppression, activities in host anti-tumor response.
Treatment of green tea saponin also was found to induced cytotoxicity to EL4 cancer cell line without causing harm to healthy cells.
The efficacy of tea saponin in inhibition of the proliferation and invasiveness of T-lymphoma (EL4) cells, may be attributed to the effect of others inflammatory cytokines such as tumor necrosis factor alphaTNF-α(26)in induced cancer cells death and NF-κB(26) in controlled transcription of DNA, cytokine production and cell survival through mediated the regulation of MAPK pathway(26) in transduction (process by which foreign DNA is introduced into a cell by a virus or viral vector) and extracellular signals to cellular responses in induction of cell proliferation, differentiation, development, transformation, and apoptosis.
Tumor necrosis factor alpha TNF-α, a pro-inflammatory cytokine plays an important role in the acute phase of inflammation with function in regulation of biological processes of cell proliferation, differentiation and apoptosis.
Nuclear factor-κB (NF-κB) is a transcription factor with function in regulated expression of genes involving many biological processes including innate and adaptive immunity, inflammation and stress responses,
In NOD/SCID mice transplanted intraperitoneally with human non-Hodgkin's lymphoma (NHL) cell lines Namalwa, RAP1-EIO and HS-Sultan, injection of green tea displayed a significant inhibition of
50% of Namalwa tumors and RAP1-EIO and HS-Sultan tumor(27) through paralyzed tumor invasive activities.
In compared to chemotherapy drug cyclophosphamide, green tea exhibited anti-angiogenic effect in induction of.frequency of apoptotic endothelial and tumor cell and promoted tumor shrinking(27) by blocking the formation of new blood vessels in providing nutrients and fluid for tumor expansion.
11. Endometrial Cancer
In the experiment of green tea bioactive compound against progression of tumor xenografts of human endometrial cancer, (-)-epigallocatechin-3-gallate EGCG demonstrated a significant effect in reduced risk of endometrial cancer development(28) through the bioactive chemicals anti tumor angiogenesis properties.
The anti cancer active compound efficacy was attributed to the modulation of expression of vascular endothelial growth factor A (VEGFA) protein(28) in the established new vessel to stimulate the onset of cancer and cancer cell proliferation and HIF-1 functions(28) in activated transcription of many genes, in regulated cellular and systemic homeostatic response to external changes to tumor growth.
Application of EGCG also suppressed responses of chemokine (C-X-C motif) ligand 12 (CXCL12)(28) in expression of multiple physiological processes, in promoted invasion and metastasis of tumor cells in connected tissues of the uterine mucosa(28) (endometrium), thus reducing the infiltration of VEGFA-expressing tumor-associated macrophages (TAMs)(28) in supplying rapidly growing malignant tissues with essential nutrients and oxygen.
Further analysis also insisted that EGCG restricted secretion of vascular endothelial growth factor A (VEGFA) in initiated endometrial cancer growth by inhibiting the function of PI3K/AKT/mTOR/HIF1α pathway(29) in regulated many cellular processes, including cell survival, proliferation, and growth.
After taking account of all findings, treatment with EGCG reduced risk of endometrial cancer onset may be results of EGCG suppressed secretion in both fronts including decreased cancer cell-secreted VEGFA(29) but inhibited TAM-secreted VEGFA(29) in endometrial cancer progression.
Green tea polyphenol (-)-epigallocatechin-3-gallate reduced cancer expansion in suppressing the expression of proliferation markers, by acting indirectly to stimulate endometrial epithelial proliferation in estrogen receptor α, progesterone receptor, proliferating cell nuclear antigen and cyclin D1(29).
The overexpression of cyclin D1 has been linked to the development and progression of cancer.
Proliferating cell nuclear antigen is a protein with function in cell cycle regulation and/or DNA replication and important for both DNA synthesis and DNA repair.
The inhibition of EGCG also decreased the activation of ERK, the extracellular signal–regulated kinases protein(29) in cancer cell division and down expression of transcription factors fos and jun(29), the cellular immediate-early genes in induced transient cancer cell division and differentiation processes.
The function of EGCG in reduced risk of endometrial cancer also expressed through Bcl-2-associated X protein(29), cleavage of caspase-3 and poly(ADP-ribose) polymerase actions(29) in induction of cancer cell apoptosis and suppression of antiapoptotic protein Bcl-2 (B-cell lymphoma 2).
Bcl-2-associated X is a protein with function of anti- or pro-apoptotic regulators involved in a wide variety of cellular activities.
B-cell lymphoma 2, a family protein with function in regulation of cell apoptosis.
Cleavage of caspase-3 also is known as a critical executioner of apoptosis,
Poly(ADP-ribose) polymerase is a protein with function involved in a number of cellular processes, including programmed cell death.
Implicitly, application of EGCG also increased production of free radical expression in initiated the cytoxicity effect by reduced levels of antioxidant glutathione levels and activated the p38(29) in cancer cells death without inducing toxicity to normal cells
P38 mitogen-activated protein kinases (MAPKs) are activated by a wide range of cellular stresses as well as in response to inflammatory cytokines involved in cell differentiation, apoptosis and autophagy.
According to a systematic review of literature published on database of PubMed, Embase, Cochrane Library and China Biological Medicine Database upto February 2, 2015, green tea consumption was associated with a reduced risk of EC with a relative risk of .78 and each additional cup of green tea consumed per day decreased risk of developing EC by 11%(30).
Particularly, intake of green tea associated to attenuated risk of endometrial cancer was 84.33% in compared to 5.07 % of black tea(30).
12. Esophageal Cancer
According to statistic, 2,300 Canadians will be diagnosed with esophageal cancer in 2017.
In esophageal cancer cell lines Eca109 and Ec9706, injection of green tea EGCG plus chemodrug adriamycin (ADM) after 24 hours displayed a significantly increased cellular apoptosis(31).
According to flow cytometry assay, the application induced the elevation of ROS and ADM concentration in production of toxicity(31) to counter the reaction of tumor cell in diminished expression of mitochondrial membrane potential and ABCG2 protein to induce apoptosis(31).without harming to healthy cells.
ABCG2 protein expression plays a major role in multi-drug resistance, produced by tumor cells to accounter reaction to chemo-medicine.
Mitochondrial membrane potential is a central intermediate in oxidative energy metabolism, the deceased levels caused by toxicity ROS may result in energy deletion and subsequently, causing cells death.
EGCG also inhibited the growth of Eca109 and Ec9706 cells through ameliorated the anti apoptotic bcl-2 protein expression(31) and promoted bax(31) and caspase-3 protein expressions(31) with functions in induced apoptosis in a dose- and time- dependent manner.
BCL2 family members form hetero- or homodimers and plays an important anti-apoptotic protein.
Caspase-3 protein.plays a central role in the execution-phase of cell apoptosis.
BAX gene, is a member of the Bcl-2 gene family plays an important role in mediation of cell death by apoptosis.
Compared to ADM treatment alone, the Eca109/ABCG2 multi-drug resistance cancer cells, rate of apoptosis and ADM concentration were significant higher in mitochondrial membrane potential in compared to ABCG2 expression(32).
In other word, injection of green tea plus ADM was more effective in induced cells death in Eca109/ABCG2 multi-drug resistance cancer cells with expression ROS and ADM in enhanced elevation cytotoxity activity in compared to ADM treatment alone.
After taking into account of others confounders, Dr, Liu L the lead author (32)said, " EGCG inhibited cell growth and induced esophageal cancer cell apoptosis. It reduced the bcl-2 protein expression and increased the bax and caspase-3 protein expression. EGCG reversed multi-drug resistance by reducing ABCG2 expression and increasing the anticancer drug concentration in cancer cells".
In esophageal squamous cell carcinoma, application of Epigallocatechin-3-gallate (EGCG) without ADM measured by flow cytometry assay, after 24 hours also inhibited cancer site proliferation by increased expression of ROS(33) to attenuate mitochondrial membrane potential function in energy metabolism and caspase-3 protein(33) to cause malignant cellular apoptosis, in a dose-and time-dependent manner.
PCR-TRAP argentation analysis during the experiment, EGCG also demonstrated a strong inhibition of the viability of Eca109 and Ec9706 cells(33) by suppressing cancer cell in alternated DNA transcript through telomerase activity.
The continuation of study of epigallocatechin-3-gallate (EGCG) on the human esophageal cancer cell line ECa109 also discover that EGCG demonstrated a decrease of cancer cell viability but a substantial rate of apoptosis was caused by increased expression of p16 gene demethylation in induced cancer cell cycle arrest and apoptosis through level p16 mRNA expression in suppressed tumor progression of invasive and aggressive behavior(33).and p16 protein expression in promoted tumor suppressible activity, in a dose- and time-dependent manner.
P16 gene demethylation plays an important role in cell cycle arrest and apoptosis. gene alternation was found in several types of cancer.
Low level of p16 mRNA expression is associated to progression of cancer with malignant and aggressive behavior.
Abnormalities of p16 gene and loss of p16 protein expression may be related to the pathogenesis and development of some cancers.
13. Bladder Cancer
According to statistic provided by cancer.net, 90% of people with bladder cancer are older than 55, and the average age of people diagnosed with bladder cancer is 73
In T24 human bladder cancer cell line, application of the chemopreventive/antiproliferative potential of (-)-epigallocatechin gallate (EGCG, the major phytochemical in green tea) induced anti malignant cell proliferation by modulating the expression of phosphatidylinositol 3' kinase/Akt in activated Bcl-2 family proteins(34)with function in regulation of cell death, thus enhancing apoptosis of T24 bladder cancer cell line in dose- and time-dependent manner.
The phosphatidylinositol 3'-kinase/AKT pathway is a crucial regulator of cellular processes including cell proliferation and apoptosis.
Bcl-2 family proteins is a modulator responsible for regulation of cell apoptosis.
In C3H/HeN mice subcutaneously implanted with MBT-2 murine bladder tumor cells, administration of EGCGs physically attached onto the surface of nanogold particles pNG(EGCG-adsorbed pNG) exerted a significant anti cancer proliferation through induction of apoptosis(35).
This action of anti cancer effect was attributed to mechanism of EGCG-pNG in activation of caspases which play an important role in induced cell apoptosis and inflammation through Bcl-family proteins(35) with function in control apoptosis by activating caspase proteases in the governing the space between outer and inner mitochondrial membrane.
Under stress, the mitochondrial pathway or the intrinsic pathway is activated depending to the release of proteins from the intermembrane space of mitochondria.
Caspase cascade, a family protease enzymes with function in programmed cell death and inflammation.
Injecting EGCG-pNG directly into the tumor site inhibited tumor expansion also ameliorated the function of vascular endothelial growth factor (VEGF)(35) in stimulated formation of new blood vessel in provided nutrients and oxygen for survival of cancer site in compared to
oral administration of EGCG in stimulated immune function in suppression of cancer progression.
Vascular endothelial growth factor, is a signal protein produced by cells in stimulated formation of blood vessel for cell division and site proliferation.
Based on information collected,, the prepared EGCG-pNG was more effective than free EGCG in inhibiting bladder tumor in model mice.
In bladder tumor induced by N-butyl-(-4-hydroxybutyl) nitrosaminre (BBN) 0.05% solution on 8 week-old female C3H/He mice for 14 or 24 weeks on treatment with or without green tea polyphenols (GTP) expressed a significant lower rate of tumor invasive frequency of 23.8%(36) in group treated with both GTP and BBN in compared to 65.2% in group treated with BBN alone(36).
The tumorvolume and microvascular density (MVD) as an independent predictor within a tumor.and the connective, functionally supportive framework of a biological cell, tissue, or organ region in the BBN+GTP group were also significantly lower than in BBN treated mice.
Green tea polyphenols inhibited tumor growth and invasion in mice with established bladder cancer through regulation of angiogenetic effect(36) in suppressed the forming of new blood vessel for the tumor cells proliferation, metastatic spread, as well as providing oxygen and nutrients and removal of waste products of cancer cells without exhibiting anti-carcinogenic effect.
14. Pancreatic Cancer
According to statistic, the average lifetime risk of pancreatic cancer for both men and women is about 1 in 65.
In human pancreatic ductal adenocarcinoma (PDAC) cell lines PancTu-I, Panc1, Panc89 and BxPC3, to compare the inhibited effect of EGCG to 2 components of catechins, namely, catechin gallate (CG) and epicatechin gallate (ECG), application of green tea 2 catechins components demonstrated a strong effect in inhibited proliferation(37) of PDAC cells in a dose- and time-dependent manner.
In comparison test, green tea CG and ECG exerted much stronger anti-proliferation effects than those of EGCG(37).
The proliferation of PancTu-I cells retained by green tea catechin was attributed to the antioxidant effect in interference of the cancer cell division cycle through mediating the cytokines in modulation of cell cycle regulatory proteins, such as cyclins(37), a cell division regulators, cyclin-dependent kinase (Cdk) enzymes(37) activated by cyclins(37) in regulated cell progression through cell cycle arrest, and CDK inhibitors(37) with function in prevented over proliferation of cancer cells.
All 3 components of green tea catechins also demonstrated a substantiated effect in ameliorated secretion of pro-inflammatory and invasion promoting proteins of the cancer cell through expression of TNF tumor necrosis factor(37) in activated of the nuclear factor NF-κB protein signalling(37) involved mediation of DNA transcript, pro inflammatory cytokines production and cancer cell survival.
Tumor necrosis factor is a cell-signaling protein possessed a wide range of proinflammatory actions
NF-κB is a protein with function in controlled transcription of DNA, cytokine production and cell survival.
Once again, green tea catechins ECG and CG exhibit potent and much stronger anti-proliferate and anti-inflammatory activities on PDAC cells(37) in compared to EGCG
In human pancreatic cancer cells lines MIA PaCa-2 cells, injection of green tea EGCG plus Bleomycin, (BLM), an anti-cancer chemotherapeutic drug displayed a substantial effect in inhibited cell proliferation through cell cycle transition phase arrest and mitochondrial depolarization by mitochondrial permeability transition in induction of cell apoptosis, after 72 hours(38).
EGCG and BLM exhibited anti-proliferative effects significantly in induced apoptosis of MIA PaCa-2 cells(38) and suggested that this combination could represent a new strategy with potential advantages for treatment of pancreatic cancer.
In pancreatic cancer cell lines MIA PaCa-2 and PANC-1, injection of pterostilbene isolated from blue berry and EGCG expressed a strongly additive antiproliferative effect after 72 hours with MIA(39) underwent S-phase arrest but not in cancer cell line PANC-1(39).
Both pterostilbene and EGCG induced mitochondrial depolarization in enhanced cytochrome c released from mitochondria(39) to trigger programmed cell death during the early stages of apoptosis was observed also in MIA, but not in PANC
EGCG increased caspase-3/7 function in induced cell apoptosis in MIA(39) but the combined treatment did not significantly increase the activity in either cell lines.(39) these contradictory activities may indicate that cell death occurs in MIA, possibly through another mechanism.
15. Kidney Cancer
According to statistic, kidney cancer is very uncommon in people younger than age 45 and among the 10 most common cancers in both gender.
In 250 newly diagnosed, histo-logically confirmed Clear cell renal cell carcinoma (CCRCC) cases and 299 sex-, age-matched healthy controls provided complete information by face-to-face interview in Shanghai between 2007 and 2009, application of green tea at dose of ≥500 ml/d demonstrated a significantly inverse association to risk of CCRCC(40).
Green tea consumption of lower than the said volume such as 8 oz (237 ml) or more cups/day was also associated to decrease renal cell cancer risk, in compared to non drinkers, according to the report of Brigham and Women's Hospital and Harvard Medical School.
CCRCC risk induced by interaction with the environmental exposures association to polymorphisms of the xenobiotic-metabolizing enzymes also inhibited by green tea extract through increasing serum and liver antioxidant capacity and strengthening stability of microsomal and lysosomal membranes of healthy cells in compared to control(41).
In free radical aspect, the examine Wistar rats induced renal cancer pre-treated with N-ethyl-N-hydroxyethylnitrosamine (EHEN) by oral injection of drinking water for 2 weeks, also found that administration of green tea extract catechin ( 0.1% polyphenon-60) over 30 weeks of period of treatment exhibits a significant effect in decreased the incidence of renal cell tumors greater than 3 mm in diameter(42) but not tumors that are less than 3 mm in diameter942), through over expression of antioxidant in suppression of reactive oxygen species (ROS) induced by N-ethyl-N-hydroxyethylnitrosamine (EHEN) pre-treatment(42).
In alternated gene expression increased prevalence of cancer in human subjects, application of green tea polyphenol, catechins reverse change of DNA methylation in contributed to the tumor repressive gene of RGS2 (regulator of G-protein signaling 2) in modulated expression of cancers and increased the regulation of conversion of DNA to RNA (transcription) of these genes(43) in ameliorated risk of renal and other cancer(s).
Combined application of of green tea extract bioactive catechins and epigallocatechin gallate also showed to modulate DNA methylation by attenuating the effect of DNA methyltransferase 1 (DNMT1)(43) to ensure the fidelity of replication of inherited epigenetic patterns.
Aberrant DNA methylation patterns are associated with increased prevalence of renal and other tumor(s).
16. Skin Cancer
According to statistic, approximately, 87,110 new cases of invasive melanoma are diagnosed in the U.S every years
The evaluation of green tea effect in overexposure to environmental solar ultraviolet (UV) radiation (290-400 nm) which has been found to increase risk of the development of melanoma and non-melanoma skin cancers in mice model showed that oral administration of green tea pylophenols (GTPs) in drinking water or the topical application of EGCG prevents UVB-induced skin tumor development in tested subjects(44).
(-)-Epigallocatechin-3-gallate (EGCG), the major and most photoprotective polyphenolic component of green tea exhibited a protective activity against UV in induction of skin cancer(44), through induction of immunoregulatory cytokine interleukin (IL) 12 in differentiation of naive T cells into Th1 cells(44) and acted as T cell-stimulating factor in stimulate the growth and function of T cells.
Moreover, interleukin (IL) 12 also demonstrated a significant effect as an antagonist against immunosuppression induced by solar/ultraviolet (UV) radiation(44) by restoring immune responses and also stimulating DNA repair.
Green tea (-)-Epigallocatechin-3-gallate (EGCG) inhibited UV in induction of skin tumors; angiogenetic effect(45)in stimulated production of new blood vessels to provide nutrients and oxygen for cancer cells proliferation and survivals and initiated cytotoxic T lymphocyte cells in induced cancer and infectious and damage cells apoptosis.
Additional study of green tea polyphenols (GTPs) in prevention of UVB irradiated (80 mJ/cm(2)) 3 times each week for 24 wk in induced skin cancer in mice divided in to group consumed water and group fed with water containing 2 g/L GTPs, showed that group treated with GTPs displayed a significant reduced UVB-induced tumor incidence by 35%, tumor multiplicity by 63%, and tumor growth by 55% in compared to non treatment group(46).
Group treated with GTPs+UVB also demonstrated a reduced expression of the matrix metalloproteinases (MMP)-2 and MMP-9(46), which are activators associated with progression from benign to advanced cancer and expression of specific endogenous tissue inhibitors of metalloproteinases (TIMPs), tissues inhibitor of MMP in skin tumors in compared to mice treated with UVB alone.
GTPs+UVB group also reduced expressions of CD31 and vascular endothelial growth factor(46), in activated development of new blood vessel to nourish skin tumor cells proliferation and site expansion and inhibited expression of proliferating cell nuclear antigen, a key factor in DNA replication and cell cycle regulation in skin cancer in compared to UVB group.
Mice treated with GTPs+UVB group also showed more cytotoxic CD8(+) T cells in the tumors in compared to UVB group(46) by exhibited greater activation of caspase-3 epression in induced apoptosis of the tumor cells.
17. Oral Cancer
According to statistic, 1 in 75 men and 1 in 150 women will be diagnosed with oral cancer during their lifetime.
In human oral squamous carcinoma cells (SCC-25, SCC-9), application of green tea catechin, (-)-epigallocatechin-3-gallate (EGCG) suppressed SIRT3 mRNA(47) and protein expression in induction of SCC-25 cells proliferation(47), through antioxidant effect in attenuated function of SIRT3 in contribution to cancer cell survival via mRNA transmitting by modulating oxidative stress..
Some reserachers also insisted that SIRT 3 may be considered as a bio-maker for targeting stage and grade of cancer progression.
Green tea bioactive EGCG also up regulated the nuclear localization of the estrogen-related receptor α (ERRα)(47) in inhibited oral cell carcinoma tumors by regulating SIRT3(47) in expression of cancer cellular metabolism.
EGCG application displayed a significant effect in modulated the mRNA expressions of SIRT3-associated to cancer cell in induction of cell proliferation through inhibiting the production of reactive oxidative species in precipitated chain reactive in initiation of cancer cell division.
In ROS perspective, oral administration of green tea EGCG by targeting the protein SIRT3(48) in exhibited antioxidant effect in protect healthy cells without affecting formation of ROS to facilitate oral cancer cell apoptosis through cytotoxicity(48).
Dr. Tao L(48), after taking into account of other cofounders, said, "SIRT3 represents a novel potential target through which EGCG exerts differential prooxidant effects in cancer and normal cells".
EGCG treatment increased the production of mitochondrial H2O2 in SCC-25 cells(48) within 6 hours before inducing cancer cells apoptosis.
In antioxidant activity. green extract EGCG induced differential expression of genes related to antioxidant defense in oral cancer cell and gingival fibroblasts(48), which are critical in sustaining inflammation in periodontal disease through ameliorated expression of metallothionein 3 in induction of degeneration of cells and superoxide dismutase 2/3, and thioredoxin reductase 2(48) in facilitate oxidative stress to induce oncogenesis without increased cell proliferation of human gingival fibroblast -1 (HGF-1)(48).
Additional examination indicated that the application also exhibited anti oral cancer apoptosis by increased expression of mitochondrial ROS(48) and mitochondrial dysfunction(48) in facilitated intoxicate effect without causing harm to the gingival fibroblasts through antioxidant selective activities.
Green tea with promising chemo properties due to their decreased dose and limited toxicity profiles, Dr. Ramshankar V(49), the lead author said, "It is worthwhile to include green tea extract in an oral screening program for evaluating the pre-malignant lesions comparing the results between the treated and untreated group. Given the wide acceptance of green tea, its benefits may help in effective chemo-prevention oral cancer".
Summary
Taken together, the information findings suggested that green tea and its bioactive polyphenols such as catechin, (-)-epigallocatechin-3-gallate (EGCG) may have a profound and therapeutic effect in reduced risk of various types of cancer, however, due to limitation of this review, further research and studies are necessary before green tea can be recommended as a functional food in prevented risk and adjunct therapy for treatment of cancers.
Author Biography
Kyle J. Norton (All right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.
Sources
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(2) Epigallocatechin gallate inhibits the growth of MDA-MB-231 breast cancer cells via inactivation of the β-catenin signaling pathway by Hong OY1, Noh EM2, Jang HY1, Lee YR2, Lee BK3, Jung SH3, Kim JS1, Youn HJ3.(PubMed)
(3) Green Tea Catechin, EGCG, Suppresses PCB 102-Induced Proliferation in Estrogen-Sensitive Breast Cancer Cells by Baker KM1, Bauer AC2.(PubMed)(4) Preparation of catechin extracts and nanoemulsions from green tea leaf waste and their inhibition effect on prostate cancer cell PC-3 by Tsai YJ1, Chen BH1.(PubMed)
(5)Reduced prostate cancer risk with green tea and epigallocatechin 3-gallate intake among Hong Kong Chinese men by Lee PMY1, Ng CF2, Liu ZM3, Ho WM4, Lee MK5, Wang F1, Kan HD6, He YH7, Ng SSM2, Wong SYS1, Tse LA1.(PubMed)
(6) Green tea and the risk of prostate cancer: A systematic review and meta-analysis by Guo Y1, Zhi F, Chen P, Zhao K, Xiang H, Mao Q, Wang X, Zhang X.(PubMed)
(7) Overexpression of miR-126 sensitizes osteosarcoma cells to apoptosis induced by epigallocatechin-3-gallate by Jiang L, Tao C, He A, He X1.(PubMed)
(8) Green tea polyphenol EGCG suppresses osteosarcoma cell growth through upregulating miR-1 by Zhu K1, Wang W2.(PubMed)
(9) Tumoricidal effects of a selenium (Se)-polysaccharide from Ziyang green tea on human osteosarcoma U-2 OS cells by Wang Y1, Chen J, Zhang D, Zhang Y, Wen Y, Li L, Zheng L.(PubMed)(10) Green tea catechin, epigallocatechin-3-gallate, attenuates the cell viability of human non-small-cell lung cancer A549 cells via reducing Bcl-xL expression by Sonoda JI1, Ikeda R2, Baba Y3, Narumi K1, Kawachi A1, Tomishige E1, Nishihara K1, Takeda Y2, Yamada K4, Sato K5, Motoya T1.(PubMed)
(11) Gene regulation mediated by microRNAs in response to green tea polyphenol EGCG in mouse lung cancer by Zhou H, Chen JX, Yang CS, Yang MQ, Deng Y, Wang H.(PubMed)
(12) Green tea extract induces protective autophagy in A549 non-small lung cancer cell line by Izdebska M1, Klimaszewska-Wiśniewska A1, Hałas M1, Gagat M1, Grzanka A1.(PubMed)
(13) Hyaluronic acid-green tea catechin micellar nanocomplexes: Fail-safe cisplatin nanomedicine for the treatment of ovarian cancer without off-target toxicity by Bae KH1, Tan S1, Yamashita A1, Ang WX1, Gao SJ1, Wang S1, Chung JE1, Kurisawa M2.(PubMed)
(14) Epigallocatechin-3-gallate delivers hydrogen peroxide to induce death of ovarian cancer cells and enhances their cisplatin susceptibility by Chan MM1, Soprano KJ, Weinstein K, Fong D.(PubMed)
(15) Anticancer effects of (-)-epigallocatechin-3-gallate on ovarian carcinoma cell lines by Huh SW1, Bae SM, Kim YW, Lee JM, Namkoong SE, Lee IP, Kim SH, Kim CK, Ahn WS.(PubMed)(16) Epigallocatechin-3-gallate(EGCG) suppresses melanoma cell growth and metastasis by targeting TRAF6 activity by Zhang J1,2, Lei Z1,2, Huang Z3, Zhang X1,2, Zhou Y1,2, Luo Z1,2, Zeng W1,2, Su J1,2, Peng C1,2, Chen X1,2.(PubMed)
(17) EGCG enhances TRAIL-mediated apoptosis in human melanoma A375 cell line by Shen Q1, Tian F, Jiang P, Li Y, Zhang L, Lu J, Li J.(PubMed)
(18) Epigallocatechin-3-O-gallate up-regulates microRNA-let-7b expression by activating 67-kDa laminin receptor signaling in melanoma cells by Yamada S1, Tsukamoto S1, Huang Y1, Makio A1, Kumazoe M1, Yamashita S1, Tachibana H1.(PubMed)
(19) Tea polyphenols EGCG and TF restrict tongue and liver carcinogenesis simultaneously induced by N-nitrosodiethylamine in mice by Sur S1, Pal D2, Roy R2, Barua A2, Roy A3, Saha P2, Panda CK4.(PubMed)
(20) Tea polyphenols epigallocatechin gallete and theaflavin restrict mouse liver carcinogenesis through modulation of self-renewal Wnt and hedgehog pathways by Sur S1, Pal D2, Mandal S3, Roy A4, Panda CK5.(PubMed)(21) (-)-Epigallocatechin-3-gallate inhibits VEGF expression induced by IL-6 via Stat3 in gastric cancer by Zhu BH1, Chen HY, Zhan WH, Wang CY, Cai SR, Wang Z, Zhang CH, He YL.(PubMed)
(22) [(-)-Epigallocatechin-3-gallate reduces vascular endothelial growth factor expression in gastric cancer cells via suppressing activity].[Article in Chinese] by Zhu BH1, He YL, Zhan WH, Cai SR, Wang Z, Zhang CH, Chen HY.(PubMed)
(23) Reversal of 5-fluorouracil resistance by EGCG is mediate by inactivation of TFAP2A/VEGF signaling pathway and down-regulation of MDR-1 and P-gp expression in gastric cancer by Tang H1,2, Zeng L2, Wang J2, Zhang X2, Ruan Q2, Wang J2, Cui S2, Yang D1.(PubMed)
(24) Apoptotic effect of EGCG in HT-29 colon cancer cells via AMPK signal pathway by Hwang JT1, Ha J, Park IJ, Lee SK, Baik HW, Kim YM, Park OJ.(PubMed)
(25) Reduction in promotor methylation utilizing EGCG (epigallocatechin-3-gallate) restores RXRα expression in human colon cancer cells by Morris J1, Moseley VR2, Cabang AB1, Coleman K2, Wei W3, Garrett-Mayer E4, Wargovich MJ1.(PubMed)(26) Immunomodulatory effect of tea saponin in immune T-cells and T-lymphoma cells via regulation of Th1, Th2 immune response and MAPK/ERK2 signaling pathway by Bhardwaj J1, Chaudhary N, Seo HJ, Kim MY, Shin TS, Kim JD.(PubMed)
(27) Inhibition of angiogenesis and induction of endothelial and tumor cell apoptosis by green tea in animal models of human high-grade non-Hodgkin's lymphoma by Bertolini F1, Fusetti L, Rabascio C, Cinieri S, Martinelli G, Pruneri G.(PubMed)
(28) Green tea, black tea consumption and risk of endometrial cancer: a systematic review and meta-analysis by Zhou Q1, Li H2, Zhou JG3, Ma Y4, Wu T5, Ma H6.(PubMed)
(29) A prodrug of green tea polyphenol (-)-epigallocatechin-3-gallate (Pro-EGCG) serves as a novel angiogenesis inhibitor in endometrial cancer by Wang J1, Man GCW2, Chan TH3, Kwong J1, Wang CC4.(PubMed)
(30) (-)-Epigallocatechin-3-gallate induces apoptosis in human endometrial adenocarcinoma cells via ROS generation and p38 MAP kinase activation by Manohar M1, Fatima I, Saxena R, Chandra V, Sankhwar PL, Dwivedi A.(PubMed)
(31) Epigallocatechin-3-gallate promotes apoptosis and reversal of multidrug resistance in esophageal cancer cells by Liu L1, Ju Y2, Wang J3, Zhou R3.(PubMed)
(32) Epigallocatechin-3-gallate suppresses cell proliferation and promotes apoptosis in Ec9706 and Eca109 esophageal carcinoma cells by Liu L1, Zuo J1, Wang G1.(PubMed)
(33) Epigallocatechin-3-gallate inhibits growth and induces apoptosis in esophageal cancer cells through the demethylation and reactivation of the p16 gene by Meng J1, Tong Q2, Liu X2, Yu Z3, Zhang J3, Gao B3.(PubMed)(34) A component of green tea, (-)-epigallocatechin-3-gallate, promotes apoptosis in T24 human bladder cancer cells via modulation of the PI3K/Akt pathway and Bcl-2 family proteins by Qin J1, Xie LP, Zheng XY, Wang YB, Bai Y, Shen HF, Li LC, Dahiya R.(PubMed)
(35) The treatment of bladder cancer in a mouse model by epigallocatechin-3-gallate-gold nanoparticles by Hsieh DS1, Wang H, Tan SW, Huang YH, Tsai CY, Yeh MK, Wu CJ.(PubMed)
(36) Green tea polyphenol suppresses tumor invasion and angiogenesis in N-butyl-(-4-hydroxybutyl) nitrosamine-induced bladder cancer by Sagara Y1, Miyata Y, Nomata K, Hayashi T, Kanetake H.(PubMed)
(37) Epicatechin gallate and catechin gallate are superior to epigallocatechin gallate in growth suppression and anti-inflammatory activities in pancreatic tumor cells. by Kürbitz C1, Heise D, Redmer T, Goumas F, Arlt A, Lemke J, Rimbach G, Kalthoff H, Trauzold A.(PubMed)
(38) Inhibitory effect of (-)-epigallocatechin-3-gallate and bleomycin on human pancreatic cancerMiaPaca-2 cell growth by Bimonte S#1, Leongito M#1, Barbieri A2, Del Vecchio V2, Barbieri M1, Albino V1, Piccirillo M1, Amore A1, Di Giacomo R1, Nasto A1, Granata V3, Petrillo A3, Arra C2, Izzo F1.(PubMed)
(39) Inhibitory effects of (-)-epigallocatechin-3-gallate and pterostilbene on pancreatic cancer growth in vitro by Kostin SF1, McDonald DE, McFadden DW.(PubMed)(40) Risk factor for clear cell renal cell carcinoma in Chinese population: a case-control study by Wang G1, Hou J, Ma L, Xie J, Yin J, Xu D, Chang W, Tan X, Su T, Zhang H, Cao G.(PubMed)
(41) [Effects of green tea extract and its components on antioxidant status and activities of xenobiotic metabolizing enzymes of rats] by [Article in Russian](PubMed)
Kravchenko LV, Trusov NV, Aksenov IV, Avren'eva LI, Guseva GV, Lashneva NV, Tutel'ian VA.
(42) Effect of polyphenon-60 on the development of renal cell tumors in rats treated with N-ethyl-N hydroxyethylnitrosamine byYoshioka N1, Hiasa Y, Cho M, Kitahori Y, Hirao K, Konishi N, Kuwashima S.(PubMed)
(43) Targeting DNA Methylation with Green Tea Catechins by Yiannakopoulou E.C.(Karger)
(44) Green Tea Prevents Skin Cancer by Two Mechanisms by Navid Bouzari, Yvonne Romagosa, Robert S. Kirsner(PubMed)
(45) Green tea and skin cancer: photoimmunology, angiogenesis and DNA repair by Katiyar S1, Elmets CA, Katiyar SK.(PubMed)
(46) Orally administered green tea polyphenols prevent ultraviolet radiation-induced skin cancer in mice through activation of cytotoxic T cells and inhibition of angiogenesis in tumors by Mantena SK1, Meeran SM, Elmets CA, Katiyar SK.(PubMed)(47) Differential prooxidative effects of the green tea polyphenol, (-)-epigallocatechin-3-gallate, in normal and oral cancer cells are related to differences in sirtuin 3 signaling by Tao L1, Park JY, Lambert JD.(PubMed)
(48) The role of the mitochondrial oxidative stress in the cytotoxic effects of the green tea catechin, (-)-epigallocatechin-3-gallate, in oral cells.by Tao L1, Forester SC, Lambert JD.(PubMed)
(49) Chemoprevention of oral cancer: Green tea experience by Ramshankar V1, Krishnamurthy A2.(PubMed)
The inhibition of prostate cancer cell line is observed in cell cycle arrest by regulated proteins involved cell cycle division(4), namely cyclin A, cyclin B, cyclin-dependent kinase 2, and cyclin-dependent kinase 1 expression and activated cell atopotosis and survival.
Dr. Tsai YJ, the lead author said, "Catechin extract and nanoemulsion could induce apoptosis of PC-3 cells through decrease in B-cell lymphoma 2 (bcl-2) expression and increase in cytochrome c expression( in induction of apoptosis) for activation of caspase-3, caspase-8, and caspase-9 (involved cell death)".
In the recruited 404 PCA cases and 395 controls from the same hospital to investigate whether habitual tea consumption, including green, oolong, black and pu'er tea regular green drinkers have a significantly reduced risk in prostate cancer development(5), scientists found that there are inverse relation of tea drinkers and risk of prostate cancer among the habitual pu'er tea drinkers(6)and lower intake of EGCG(5) was observed among cases (54.4 mg) than the controls (72.5 mg).
The differentiation of 7 observational studies and 3 randomized controlled trials retrieved from Cochrane Library, PubMed, Sciencedirect Online, and hand searching.the database, also revealed an interest correlated incidence of PCa decrease with each cup/day increase of green tea(6)..
According of the study(6), "higher green tea consumption was linearly reduced PCa risk with more than 7 cups/day and green tea catechins were effective for preventing PCa".
3. Osteosarcoma
Osteosarcoma is a medical condition of bone cancer characterized by producing immature bone and occurred mostly in children and young adults between the ages of 10 and 30.
According to the study in investigation of the effects of Epigallocatechin-3-gallate (EGCG), in reduced risk of osteosarcoma expression in compared to miR-126 in the proliferation, invasion, migration, and chemotherapeutics resistance in cancer(7), application of Epigallocatechin-3-gallate (EGCG) exerted a significant effect in suppresseed proliferation of human cell line osteosarcoma MG63 and U2OS cells in a concentration-dependent and time-dependent manner and inhibited cancer cell lines at the concentration of 0.05 g/L on U2OS cells equivalent to 20 μM cisplatin (DDP)(7)
In compared to green tea extract induced cell death by interfering in cell cycle arrest, miR-126, the chemo suppressor drug induced apoptosis and inhibited proliferation in U2OS cell line but without significant effects on phase 1 of cancerous cell cycle division(7).
Researchers suggested application of Epigallocatechin-3-gallate (EGCG) may increase the effect of tumor suppressing drug miR-126 and for treatment of osteosarcoma(7).
The inhibition of miR-126 osteosarcoma cells without inducing apoptosis and cells proliferation in cell cycle division(7) is attributed to the extract in target of sequences in reducing the expression of the targeted genes.
In other words, the extract can bind directly to inhibit DNA transcription and prevented mRNA in transmitting such transcription in initiated cancer development.
Other researchers suggested that the inhibition of Epigallocatechin-3-gallate (EGCG) in reduced cancerous cell death does not limit to the function of cell cycle arrest(8).
The phytochemical compoud also expressed the apoptotic effect through modulating gene expression of cancer cell line and induced degradation of cancerous cellular structure(8).
Additional evaluation of the phytochemical Epigallocatechin-3-gallate (EGCG) and the tumor suppressed drug miR-1 effect in osteosarcoma, researchers also found that Epigallocatechin-3-gallate has a profound and positive effect in improved the efficacy of miR-1 in induced cell apoptosis and proliferation observed in cancer cell lines MG-63 and U-2OS(8).
MG-63 and U-2OS treated by miR-1 and Epigallocatechin-3-gallate (EGCG) decreased c-MET expression, which is an indication of cancers development(8).
The combined application of Epigallocatechin-3-gallate (EGCG) and c-MET inhibitor (crizotinib) also displayed a significant inhibition of MG-63 and U-2OS cancer cell proliferation)8).
In the study of the effects of Se-enriched Ziyang green tea, containing chemical compound mannose, rhamnose and fucose in anti tumor activity on human osteosarcoma U-2 OS cells in vitro and in vivo, researchers found that Se-ZYTP at concentration of 25, 50, 100 and 200 μg/ml exerted a significantly inhibition of proliferation of human osteosarcoma U-2 OS cells in a concentration-dependent fashion(9).
In cancer cell line In U-2 OS cancer induced in BALB/c athymic mice model, Se-ZYTP oral administration at three doses of 100, 200 and 400mg/kg body weight (B.W.) daily for 28 days resulted in tumor regression as compared to model control without causing any serious side effects(9).
The illustration suggested that other chemical compounds found in green tea may also have the potential in suppression of proliferation and induced apoptosis of osteosarcoma.
The anti osteosarcoma activities of Se-enriched Ziyang green tea may be attributed to the stimulation in increased pro-apoptotic protein Bax expression(9)(upregulated by the tumor suppressor(9) protein p53 in induced apoptosis) and decreased expression levels of anti-apoptotic protein Bcl-2(9)(regulator proteins that regulate cell death) and NG2(9)(involved cell survival, migration and angiogenesis), some researchers suggested.
4. Lung Cancer
Lung cancer is a medical condition characterized by cells growth disorderly and uncontrollably of lung tissues.
In the study to investigate the anti lung cancer effect of Epigallocatechin-3-gallate (EGCg), the major polyphenolic compound present in green tea, after taking into account of other con founders, researchers at the joint study lead by the Kyushu University of Health & Welfare, suggested that
the phychemical induces apoptosis of lung cancer through suppression of cell division, in cell culture(10).
In human A549 human non-small-cell lung cancer cell line, EGCg inhibited cancerous cell proliferation by interfering mRNA expression in modulation of apoptotic cell death(10)
Additionally, application of 100 μM EGCg for 24 h. exhibited cancerous morphological changes, thus reducing cell proliferation(10).
The study also revealed that the efficacy of EGCg inhibited B-cell lymphoma-extra large (Bcl-xL)(10) through expression of mRNA and suppression of gene in related to cell death.
Epigallocatechin-3-gallate (EGCg) in inhibited gene expression in risk of lung cancer by binding HIF-1α, in promoted cell proliferation and anchorage-independent growth, researchers launched a study to elucidate the role of microRNA in the EGCG inhibition of tobacco carcinogen-induced lung tumors in A/J mice found that 26 potential targeted genes of the 21 microRNAs. with the mRNA expression profiles may have some implications in increased lung cancer risk(11).
Application of EGCg, indeed, demonstrated a significant effect in improved cell regulation and reduced cell proliferation through many mechanisms, including regulation of AKT pathway(11) in promoted survival and growth in response to extracellular signals and NF-κB expression(11) in cellular responses to stimuli such as stress, cytokines, free radicals, heavy metals, ultraviolet irradiation and MAP kinases(11), involved variety of fundamental cellular processes such as proliferation, differentiation, motility, stress response, apoptosis, and survival.
In other words, Epigallocatechin-3-gallate (EGCg) effect reduced risk and treatment of lung cancer is attributed to the inhibition of expression of RNA in transmitting information to proteins with function to initiated cancer cell change, including cell proliferation and apoptosis.
The findings also suggested that green tea Epigallocatechin-3-gallate (EGCg) has a strong effect in reduced risk lung cancer through both expression of mutate and cancer-related genes(11).
Mutated genes expression has been identified in contribution to cancer development and progression, therefore by target the expression of such genes may help scientists in explore the origins of abnormal gene expression in compared to normal cells.
Other researchers suggested that by targeting both DNA and RNA data to identify alternative expression of mutated gene in patients of lung cancer may open the door by offering specific treatment only for such patients.
More precisely, by identified such gene in cancer cell patients, scientist may prescribe gene targeting technology, specific medication and treatment to stop cancer from growing and spreading.
Further differentiation of the effect of green tea extract in lung cancer risk, researchers at the University in Toruń indicated that green tea extract catechins demonstrated a significant effect in inhibition of lung cancer line A549(12) independent to doses applied and increased cell and marker of cell degradation(12) and green tea extract catechins also expressed a strong protective effect in reduced self cause of toxicity(12)
This illustration indicated that green tea extract catechins exert anti lung cancer progression activity through protection against destruction and damage of redundant cellular components occurring in vacuoles within the cell without induced side effects.
5. Ovarian Cancer
In the analysis of the EGCG effects on 8 ovarian cancer cell lines (SKOV3, CAOV3, OVCAR3, OVCAR10, A2780, CP70, C30, and C200) and showed IC50s for EGCG at the micromolar range, researchers found that EGCG inhibited all ovarian cancer cell lines in dose depending manner(13).
Normal dose application of EGCG displayed a significant increase of antioxidant in reduced ROS over expression(13) of oxidative stress in inhibited ovarian cancer through cell cycle arrest in G2/M phase(13).
Administration of EGCG at common dose not only demonstrated a 6 fold increase of cisplatin potency for treatment of SKOV3, CAOV3, and C200 cells, but also attenuated the chemodrug toxicity(13).
However, the effect of EGCG on the formation of reactive oxygen species (ROS) was biphasic.
The phytochemical was shown to induce and decrease ROS formation in different doses.
Therefore, higher dose of EGCG promoted over expression of antioxidants in reduced oxidative stress may amplify the toxicity in ameliorated human cancer cells proliferation and induced apoptosis.
Dr.Bae KH, the lead author(13) said, "EGCG may accentuate oxidative stress to inhibit growth of ovarian cancer cells and sensitize them to cisplatin".
Other researchers in the study of toxicity of EGCG suggested that green tea catechin, (-)-epigallocatechin-3-O-gallate (EGCG) as a potent adjuvant to enhance the anti tumor efficacy of cisplatin while mitigating its harmful side effects through various mechanisms.
Application of EGCG showed to promote hyaluronic acid function in regulation of normal cell division and prevention of the acid in initiation of cancerous cell proliferation(14).
Hyaluronic acid, a polysaccharide molecule, plays an important role in cell proliferation and migration, and may involve in the progression of some malignant tumors.
Additionally, EGCG also expressed anti cancer effect by promoting the injection of chemo medicine cisplatin into the CD44-over expressing(14) cancer cells to prevent over growth of tumor cells.
In regard to toxicity, EGCG on one hand, reduced capacity of oxidative stress in initiated toxicity against off-target organs and tissues through induction of significant antioxidant activity(14) on the hand, and stimulated function of toxicity originating from cisplatin into the target tumors.
Green tea catechin-based micellar nanocomplexes also inhibited superiorly against tumor growth with no injection of cisplatin(14) and expressed a significant inhibition without induced toxicity in both cancer cells suspended in culture medium and injected into the animal models and peritoneal metastatic model of human ovarian cancer(14).
In other words, green tea catechin-based micellar nanocomplexes may be considered as a safe and effective cisplatin nanomedicine for ovarian cancer treatment..
In the additionally examined the effect of EGCG in suppressing ovarian cancer cell growth in 3 human ovarian cancer cell lines (p53 negative, SKOV-3 cells; mutant type p53, OVCAR-3 cells; and wild type p53, PA-1 cells),
EGCG decreased tumor growth in each cell line in a dose-dependent fashion and induced apoptosis and cell cycle arrest, particular to the G(1) phase in SKOV-3 and OVCAR-3 cells in compared to G(1)/S transition phase arrest in PA-1 cells(15).
The chemical also acted differentiately in upregulated the expression of genes and proteins in promoted cancer cell arrest, suppressed tumor growth and induced cell death(15) (Bax, p21, Retinoblastoma, cyclin D1, CDK4, Bcl-X(L)) by more than 2-fold.
6. Melanoma
Melanoma, is a medical condition characterized by irregular cell growth of pigment-containing cells known as melanocytes.
According to the study, approximately 7,200 Canadians will be diagnosed with melanoma skin cancer.
In the review of literature published online, green tea bioactice EGCG significantly inhibited the growth, migration and invasion of melanoma cells through numbers of mechanism.
Gene implications in initiated cancer development and cancerous cells proliferation have gone through extensive research, particularly in melanoma.
In melanoma, green tea biactice EGCG demonstrated a significant effect in knockdown gene over expression (TRAF6)(16) in reduced migration and invasion of melanoma.
TRAF6 is a protein with function in activation of IkappaB kinase (IKK) in response to inflammation.
Green tea biactive EGCG directly bound to TRAF6 in melanoma in attenuated the interaction of
between TRAF6 and UBC13(E2) in activated the protein(16) (IkappaB kinase (IKK)) in production of pro inflammatory cytokins.
The ubiquitin-conjugating enzyme(UBC13(E2)) are essential in activation protein (NF- kappa B) in controls transcription of DNA, cytokine production and cell survival.
The phytochemicals also suppressed the TRAF6 E3 ubiquitin ligase activity of the tumor generated by TRAF6(16) in regulation of important biological processes, particularly, in cell division and for the survival of the tumors.
Green tea biactice EGCG also regulated the gene expression of proteins (IκBα and p-TAK1 e) in modulated and inactivated NF-κB-directed gene expression(16) of inflammation, immunity, cell proliferation, differentiation, and survival in melanoma.
Dr. Zhang J(16), the lead author said, "EGCG is a novel E3 ubiquitin ligase inhibitor that could be used to target TRAF6 for chemotherapy or the prevention of melanoma".
Other researchers in focus of Green tea polyphenol (-)-epigallocatechin-3-O-gallate (EGCG) effect in attenuated and treatment of melanoma in the gene implication via MicroRNAs (17)(miRNAs, non-coding RNAs involved in various biological processes by regulating their target genes) also indicated that green tea polyphenol (-)-epigallocatechin-3-O-gallate (EGCG) inhibited melanoma tumor growth by activating 67-kDa laminin receptor (67LR) signaling(17) which has an function in down regulated tumor cell proliferation and tumor formation by inducing apoptosis.
The bioactive compound also up-regulated miRNA-let-7b expression in induced tumor suppressor function in decrease function of 67LR in enhanced invasive and metastatic melanoma cells.
Indeed, green tea EGCG-also displayed a significant effect in promote function of let-7b in altering the traits,of malignant cell in melanoma through regulating the expression of HMGA2.with action as DNA transcriptional regulator(17).
Green tea EGCG. also induced expression of let-7b in inhibitions of oncoproteins and activation of tumor suppressor via tumor-over expressed 67LR in activation of PP2A(17), a tumor suppressor. through adenylate cyclase/cAMP pathway in cell communication.
In compared the effects of TNF-related apoptosis-inducing ligand (TRAIL), a protein with function in in induced tumor cells apoptosis. and green tea bioactive EGCG effects in A375 melanoma cell line, researchers found that TRAIL application group demonstrats a strong effect in inhibition with apoptosis rate was 11.8% at dose of 150ng/mL in compared to green tea EGCG treatment group of 5%-7%(18).
In combined TRAIL and green tea EGCG treatment groups, the inhibited rate increased sufficiently to 48.9 - 59.1%(18) and EGCG effective in treatment of melanoma was attributed to activity of caspase-3 rather than caspase-8 in mediation of programmed cell death (apoptosis)(18).
7. Liver Cancer
In liver cancer animal model induced by chronic exposure of N-nitrosodiethylamine (NDEA), a carcinogenic and mutagenic organic compound, application of green tea bioactive compounds Epigallocatechin gallate (EGCG) and Theaflavin (TF) demonstrated a strong effect in reduced initiation of cancer formation(19) and potential chemopreventive effect in pre and post treatment(19) of the injected animal.
EGCG/TF action in restrain the over expression of liver cancer cells proliferation was the result of modulated similarly to those of CD44-specific cell membrane binding combined with near-infrared irradiation in induction of cellular apoptosis(19).
High CD44-positive expression is found to associate to acute cancer cells killing.
The restriction processes of EGCG/TF in modification of onset of liver cancer development, was also found to modify multiple biogenesis involved maintaining a relatively stable equilibrium in organs tissues(self-renewal Wnt/β-catenin, Hh/Gli1 pathways)(19) in gene with implication of cell cycle progression, apoptosis and cellular transformation and cell differentiation and proliferation(Cyclin D1, cMyc and EGFR)(19) and tumor suppressor (E-cadherin)(19) during the carcinogenesis processes.
The therapeutic efficacy of tea polyphenols epigallocatechin gallete (EGCG) and theaflavin (TF) also regulated the proteins expression of cell differentiation, polarity and proliferation(the self-renewal Wnt and Hedgehog (Hh) pathways(20).during CCl4/N-nitosodiethylamine-induced mouse liver carcinogenesis.
Green tea bioactive tea polyphenols epigallocatechin gallete (EGCG) and theaflavin (TF) induced chemo preventive potential in maintain cell integrity at the 30 weeks of CCl4/N-nitosodiethylamine application.
Continuous administration of EGCG/TF exerted a strong impact in reduced proliferation and increased apoptosis(20), as well as decreased function of hepatic progenitor cells (HPCs)(20) in participated restoration of the cancerous liver tissue and population with cancer stem cell-like characteristics in liver carcinoma observed by AFP and CD44 expression(20).in CCl4/N-nitosodiethylamine-induced mouse liver carcinogenesis.
During the restriction processes of EGCG/TF, the bioactive compounds also modulated the expression of tumor progression to a more invasive phenotype(20)(phospho-β-catenin-Y-654), tumor suppressor(β-catenin)(20), the proliferation, migration and invasion of liver cancer gene(sFRP1 )(20) and gene in control tumor suppressor(β-catenin)(20).
In other words, green tea EGCG/TF inhibited the contaminated cells inflicted by injection of CCl4/N-nitosodiethylamine to prevent the initiation of liver cancer through modulation of certain gene expressions involved in liver cancer progression.
In short, the inhibition of liver carcinogenesis by EGCG/TF was attributed to reduction in hepatocyte progenitor cell and stem cell population by restoring liver cancerous cells damage through various mechanisms indicated above.
8. Gastric Cancer
According to medical literature published online, in vascular endothelial growth factor (VEGF) over expression in formation of new blood vessel to provide nutrients and fluids for the survival of gastric cancer, application of green tea (-)-Epigallocatechin-3-gallate (EGCG) restricted the pro-inflammatory cytokine interleukin-6 (IL-6)(21) induced VEGF(21) in stimulated signal protein in transmitted alternated DNA transcript and activated suppression of anti cell apoptosis transcription 3 (Stat3)(21).
Oral administration of green tea extract decreased levels of IL-6, VEGF overexpression in doses depending manner.
In compared to healthy individual, IL-6, VEGF expression were found to increase more than 2.4-fold in patients with gastric cancer(21).
The chemical compound also exhibited anti cancer progressive activity by blocking the process of complex sequence of VEGF expression in transferring faulty DNA transcription to signal proliferation of cancer cells through mRNA in protein synthesis.
In other words, green tea inhibited the progression of cancer development induced by over expression of vascular endothelial growth factor (VEGF) was total depended EGCG's DNA biding activity(21) and inhibition of Stat proteins(21) in differentiated cytoplasm into the nucleus, the important step in initiation of cancer progression.
According to experiments in vitro and vitro, EGCG also expressed a significant effect in the reduced the IL-6 properties in stimulated vascular endothelial cells in promoted cancer cells proliferation and formation.
After taking into account of other con founders, Dr. Zhu BH, the lead author(21) said, "EGCG inhibits IL-6-induced VEGF expression and angiogenesis via suppressing Stat3 activity in gastric cancer, which has provided a novel mechanistic insight into the anti-angiogenic activity of EGCG".
Additionally, researchers in further illustration of the effect of EGCG (0, 5, 10, 25 or 50 μmol/L), in human gastric cancer cells (AGS) caused by IL-6 (50 μg/L) suggested that interleukin 6 (IL-6)over expression not only significantly increased VEGF expression in AGS gastric cancer cells, but also increased function of mRNA expression by more than 2.4 fold(22) in the process to initiated tumor development, in dose depending manner.
Treatment of bioactive EGCG with doses of 0, 5, 10, 25 or 50 μmol/L demonstrated a therapeutic activities in reduced the release protein of VEGF to stimulated and mRNA expression of alternated transcript.
In compared to AG490, a Stat3 pathway inhibitor used for treatment of gastric cancer, green tea EGCG blocked the sequence of transcript transferred step in induced expression of pSTAT3(22) in proliferation of cells and tumor tissues without causing change in STAT3 gene(22).
In 5-FU resistance of GC SGC7901/FU and MGC803/FU, gastric cancer cell lines, injection of epigallocatechin gallate (EGCG) displayed a significantly suppressed the proliferation and tumor growth through reversed the 5-FU(23) resistance of GC cells via inhibited the P-glycoprotein 1 (MDR1)(23) and P-glycoprotein (P-gp)(23) also known as multidrug resistance proteins in transmitted transcript in obstructing cell internalization of chemotherapeutic agents and developing transporter mediated resistance by cancer cells during anti-tumor treatments.
9. Colon Cancer
According to the study by the University College of Medicine, Seoul, application of EGCG on HT-29 colon cancer cells showed a significant effect in inhibition of cell cycle progression of protein in COX-2 expression(24) through activation of AMPK activity(24) in promoted metabolic tumor suppressor by regulating energy levels, enforcing metabolic checkpoints and inhibiting cell growth.
Cyclooxygenase(COX)-2, is an enzyme with function in speeding up the production of hormone prostaglandins in regulated cell proliferation and cell apoptosis.
AMPK(5' AMP-activated protein kinase) plays a role in cellular energy homeostasis, activation of AMPK(24) may result in tumor growth inhibition, cell cycle arrest, and apoptosis of cancer cells in some tumor types/contexts.
In inhibition of COX-2 expression, green tea EGCG reduced prostaglandin E(2) secretion(24), thus reducing risk of the hormone)(24) in modulated angiogenesis, including the process of new blood vessel formation, promoted proliferation, migration and formation of endothelial cells, lining the interior surface of blood vessels and lymphatic vessels.
The study also emphasized that inhibiting AMPK by an AMPK inhibitor may interrupt the function of the bioactive compound in initiated such changes(24).
Continuously, the activation of enzyme AMPK also had a strong implication on VEGF(24) (vascular endothelial growth factor) and glucose transporter in facilitated Glut-1(24) in transport of glucose across the plasma membranes of mammalian cells in EGCG-treated cancer cells.
Application of EGCG activated AMPK enzyme also modulated the production of ROS without causing ROS expression in initiated tumor progression and damage to cellular structures(24), such as the lipid membrane, protein and nucleic acid but inducing cancer cells DNA mutations and compromised genome integrity, subsequently in cancer cells senescence and death.
In other aspect of study of colon cancer in animal model, diminished levels of retinoid X receptor-alpha (RXRα) in regulated cancer cell growth and modulated suppress tumorigenesis may have a profound effect in cell proliferation.
Application of green tea bioactive EGCG expressed a significant effect in restored RXRα protein and expression levels caused by methylation function in alternated the activity of a DNA segment(25) without changing the sequence, thus reducing risk of cancer expansion.
Additional differentiation also suggested that EGCG induced methylation changes in several other colon cancer related genes to restore the levels of RXRα without causing a decrease in global methylation(25) in maintaining the epigenetic state of individual genes.
Change of globe methylation expression is found to associate to the occurrence of cancer.
Retinoid X receptor-alpha (RXRα) is a nuclear receptor with function in regulated cancer proliferation and modulated suppression of tumorigenesis.
10. Lymphoma
In EL4 cancer cells line, injection of green bioactive saponin stimulated the immunomodulatory activity in inhibited EL4 cells line through regulated cytokine expression induced by inflammation and mitogen-activated protein kinases (MAPK) signaling pathway(26) involved in a variety of fundamental cellular processes such as proliferation, differentiation, motility, stress response, apoptosis, and survival.
Furthermore, injected saponin also reduced the expression of EL4 cells line in tumor proliferation by interrupting the process of sequence of mutated DNA transcript in mRNA expression in transmitting transcript by initiating production of inflammatory cytokines to reverse transcription polymerase chain reaction in making copies of alternated gene(26), thus attenuating risk of tumor growth, tumor progression and immuno-suppression, activities in host anti-tumor response.
Treatment of green tea saponin also was found to induced cytotoxicity to EL4 cancer cell line without causing harm to healthy cells.
The efficacy of tea saponin in inhibition of the proliferation and invasiveness of T-lymphoma (EL4) cells, may be attributed to the effect of others inflammatory cytokines such as tumor necrosis factor alphaTNF-α(26)in induced cancer cells death and NF-κB(26) in controlled transcription of DNA, cytokine production and cell survival through mediated the regulation of MAPK pathway(26) in transduction (process by which foreign DNA is introduced into a cell by a virus or viral vector) and extracellular signals to cellular responses in induction of cell proliferation, differentiation, development, transformation, and apoptosis.
Tumor necrosis factor alpha TNF-α, a pro-inflammatory cytokine plays an important role in the acute phase of inflammation with function in regulation of biological processes of cell proliferation, differentiation and apoptosis.
Nuclear factor-κB (NF-κB) is a transcription factor with function in regulated expression of genes involving many biological processes including innate and adaptive immunity, inflammation and stress responses,
In NOD/SCID mice transplanted intraperitoneally with human non-Hodgkin's lymphoma (NHL) cell lines Namalwa, RAP1-EIO and HS-Sultan, injection of green tea displayed a significant inhibition of
50% of Namalwa tumors and RAP1-EIO and HS-Sultan tumor(27) through paralyzed tumor invasive activities.
In compared to chemotherapy drug cyclophosphamide, green tea exhibited anti-angiogenic effect in induction of.frequency of apoptotic endothelial and tumor cell and promoted tumor shrinking(27) by blocking the formation of new blood vessels in providing nutrients and fluid for tumor expansion.
11. Endometrial Cancer
In the experiment of green tea bioactive compound against progression of tumor xenografts of human endometrial cancer, (-)-epigallocatechin-3-gallate EGCG demonstrated a significant effect in reduced risk of endometrial cancer development(28) through the bioactive chemicals anti tumor angiogenesis properties.
The anti cancer active compound efficacy was attributed to the modulation of expression of vascular endothelial growth factor A (VEGFA) protein(28) in the established new vessel to stimulate the onset of cancer and cancer cell proliferation and HIF-1 functions(28) in activated transcription of many genes, in regulated cellular and systemic homeostatic response to external changes to tumor growth.
Application of EGCG also suppressed responses of chemokine (C-X-C motif) ligand 12 (CXCL12)(28) in expression of multiple physiological processes, in promoted invasion and metastasis of tumor cells in connected tissues of the uterine mucosa(28) (endometrium), thus reducing the infiltration of VEGFA-expressing tumor-associated macrophages (TAMs)(28) in supplying rapidly growing malignant tissues with essential nutrients and oxygen.
Further analysis also insisted that EGCG restricted secretion of vascular endothelial growth factor A (VEGFA) in initiated endometrial cancer growth by inhibiting the function of PI3K/AKT/mTOR/HIF1α pathway(29) in regulated many cellular processes, including cell survival, proliferation, and growth.
After taking account of all findings, treatment with EGCG reduced risk of endometrial cancer onset may be results of EGCG suppressed secretion in both fronts including decreased cancer cell-secreted VEGFA(29) but inhibited TAM-secreted VEGFA(29) in endometrial cancer progression.
Green tea polyphenol (-)-epigallocatechin-3-gallate reduced cancer expansion in suppressing the expression of proliferation markers, by acting indirectly to stimulate endometrial epithelial proliferation in estrogen receptor α, progesterone receptor, proliferating cell nuclear antigen and cyclin D1(29).
The overexpression of cyclin D1 has been linked to the development and progression of cancer.
Proliferating cell nuclear antigen is a protein with function in cell cycle regulation and/or DNA replication and important for both DNA synthesis and DNA repair.
The inhibition of EGCG also decreased the activation of ERK, the extracellular signal–regulated kinases protein(29) in cancer cell division and down expression of transcription factors fos and jun(29), the cellular immediate-early genes in induced transient cancer cell division and differentiation processes.
The function of EGCG in reduced risk of endometrial cancer also expressed through Bcl-2-associated X protein(29), cleavage of caspase-3 and poly(ADP-ribose) polymerase actions(29) in induction of cancer cell apoptosis and suppression of antiapoptotic protein Bcl-2 (B-cell lymphoma 2).
Bcl-2-associated X is a protein with function of anti- or pro-apoptotic regulators involved in a wide variety of cellular activities.
B-cell lymphoma 2, a family protein with function in regulation of cell apoptosis.
Cleavage of caspase-3 also is known as a critical executioner of apoptosis,
Poly(ADP-ribose) polymerase is a protein with function involved in a number of cellular processes, including programmed cell death.
Implicitly, application of EGCG also increased production of free radical expression in initiated the cytoxicity effect by reduced levels of antioxidant glutathione levels and activated the p38(29) in cancer cells death without inducing toxicity to normal cells
P38 mitogen-activated protein kinases (MAPKs) are activated by a wide range of cellular stresses as well as in response to inflammatory cytokines involved in cell differentiation, apoptosis and autophagy.
According to a systematic review of literature published on database of PubMed, Embase, Cochrane Library and China Biological Medicine Database upto February 2, 2015, green tea consumption was associated with a reduced risk of EC with a relative risk of .78 and each additional cup of green tea consumed per day decreased risk of developing EC by 11%(30).
Particularly, intake of green tea associated to attenuated risk of endometrial cancer was 84.33% in compared to 5.07 % of black tea(30).
12. Esophageal Cancer
According to statistic, 2,300 Canadians will be diagnosed with esophageal cancer in 2017.
In esophageal cancer cell lines Eca109 and Ec9706, injection of green tea EGCG plus chemodrug adriamycin (ADM) after 24 hours displayed a significantly increased cellular apoptosis(31).
According to flow cytometry assay, the application induced the elevation of ROS and ADM concentration in production of toxicity(31) to counter the reaction of tumor cell in diminished expression of mitochondrial membrane potential and ABCG2 protein to induce apoptosis(31).without harming to healthy cells.
ABCG2 protein expression plays a major role in multi-drug resistance, produced by tumor cells to accounter reaction to chemo-medicine.
Mitochondrial membrane potential is a central intermediate in oxidative energy metabolism, the deceased levels caused by toxicity ROS may result in energy deletion and subsequently, causing cells death.
EGCG also inhibited the growth of Eca109 and Ec9706 cells through ameliorated the anti apoptotic bcl-2 protein expression(31) and promoted bax(31) and caspase-3 protein expressions(31) with functions in induced apoptosis in a dose- and time- dependent manner.
BCL2 family members form hetero- or homodimers and plays an important anti-apoptotic protein.
Caspase-3 protein.plays a central role in the execution-phase of cell apoptosis.
BAX gene, is a member of the Bcl-2 gene family plays an important role in mediation of cell death by apoptosis.
Compared to ADM treatment alone, the Eca109/ABCG2 multi-drug resistance cancer cells, rate of apoptosis and ADM concentration were significant higher in mitochondrial membrane potential in compared to ABCG2 expression(32).
In other word, injection of green tea plus ADM was more effective in induced cells death in Eca109/ABCG2 multi-drug resistance cancer cells with expression ROS and ADM in enhanced elevation cytotoxity activity in compared to ADM treatment alone.
After taking into account of others confounders, Dr, Liu L the lead author (32)said, " EGCG inhibited cell growth and induced esophageal cancer cell apoptosis. It reduced the bcl-2 protein expression and increased the bax and caspase-3 protein expression. EGCG reversed multi-drug resistance by reducing ABCG2 expression and increasing the anticancer drug concentration in cancer cells".
In esophageal squamous cell carcinoma, application of Epigallocatechin-3-gallate (EGCG) without ADM measured by flow cytometry assay, after 24 hours also inhibited cancer site proliferation by increased expression of ROS(33) to attenuate mitochondrial membrane potential function in energy metabolism and caspase-3 protein(33) to cause malignant cellular apoptosis, in a dose-and time-dependent manner.
PCR-TRAP argentation analysis during the experiment, EGCG also demonstrated a strong inhibition of the viability of Eca109 and Ec9706 cells(33) by suppressing cancer cell in alternated DNA transcript through telomerase activity.
The continuation of study of epigallocatechin-3-gallate (EGCG) on the human esophageal cancer cell line ECa109 also discover that EGCG demonstrated a decrease of cancer cell viability but a substantial rate of apoptosis was caused by increased expression of p16 gene demethylation in induced cancer cell cycle arrest and apoptosis through level p16 mRNA expression in suppressed tumor progression of invasive and aggressive behavior(33).and p16 protein expression in promoted tumor suppressible activity, in a dose- and time-dependent manner.
P16 gene demethylation plays an important role in cell cycle arrest and apoptosis. gene alternation was found in several types of cancer.
Low level of p16 mRNA expression is associated to progression of cancer with malignant and aggressive behavior.
Abnormalities of p16 gene and loss of p16 protein expression may be related to the pathogenesis and development of some cancers.
13. Bladder Cancer
According to statistic provided by cancer.net, 90% of people with bladder cancer are older than 55, and the average age of people diagnosed with bladder cancer is 73
In T24 human bladder cancer cell line, application of the chemopreventive/antiproliferative potential of (-)-epigallocatechin gallate (EGCG, the major phytochemical in green tea) induced anti malignant cell proliferation by modulating the expression of phosphatidylinositol 3' kinase/Akt in activated Bcl-2 family proteins(34)with function in regulation of cell death, thus enhancing apoptosis of T24 bladder cancer cell line in dose- and time-dependent manner.
The phosphatidylinositol 3'-kinase/AKT pathway is a crucial regulator of cellular processes including cell proliferation and apoptosis.
Bcl-2 family proteins is a modulator responsible for regulation of cell apoptosis.
In C3H/HeN mice subcutaneously implanted with MBT-2 murine bladder tumor cells, administration of EGCGs physically attached onto the surface of nanogold particles pNG(EGCG-adsorbed pNG) exerted a significant anti cancer proliferation through induction of apoptosis(35).
This action of anti cancer effect was attributed to mechanism of EGCG-pNG in activation of caspases which play an important role in induced cell apoptosis and inflammation through Bcl-family proteins(35) with function in control apoptosis by activating caspase proteases in the governing the space between outer and inner mitochondrial membrane.
Under stress, the mitochondrial pathway or the intrinsic pathway is activated depending to the release of proteins from the intermembrane space of mitochondria.
Caspase cascade, a family protease enzymes with function in programmed cell death and inflammation.
Injecting EGCG-pNG directly into the tumor site inhibited tumor expansion also ameliorated the function of vascular endothelial growth factor (VEGF)(35) in stimulated formation of new blood vessel in provided nutrients and oxygen for survival of cancer site in compared to
oral administration of EGCG in stimulated immune function in suppression of cancer progression.
Vascular endothelial growth factor, is a signal protein produced by cells in stimulated formation of blood vessel for cell division and site proliferation.
Based on information collected,, the prepared EGCG-pNG was more effective than free EGCG in inhibiting bladder tumor in model mice.
In bladder tumor induced by N-butyl-(-4-hydroxybutyl) nitrosaminre (BBN) 0.05% solution on 8 week-old female C3H/He mice for 14 or 24 weeks on treatment with or without green tea polyphenols (GTP) expressed a significant lower rate of tumor invasive frequency of 23.8%(36) in group treated with both GTP and BBN in compared to 65.2% in group treated with BBN alone(36).
The tumorvolume and microvascular density (MVD) as an independent predictor within a tumor.and the connective, functionally supportive framework of a biological cell, tissue, or organ region in the BBN+GTP group were also significantly lower than in BBN treated mice.
Green tea polyphenols inhibited tumor growth and invasion in mice with established bladder cancer through regulation of angiogenetic effect(36) in suppressed the forming of new blood vessel for the tumor cells proliferation, metastatic spread, as well as providing oxygen and nutrients and removal of waste products of cancer cells without exhibiting anti-carcinogenic effect.
14. Pancreatic Cancer
According to statistic, the average lifetime risk of pancreatic cancer for both men and women is about 1 in 65.
In human pancreatic ductal adenocarcinoma (PDAC) cell lines PancTu-I, Panc1, Panc89 and BxPC3, to compare the inhibited effect of EGCG to 2 components of catechins, namely, catechin gallate (CG) and epicatechin gallate (ECG), application of green tea 2 catechins components demonstrated a strong effect in inhibited proliferation(37) of PDAC cells in a dose- and time-dependent manner.
In comparison test, green tea CG and ECG exerted much stronger anti-proliferation effects than those of EGCG(37).
The proliferation of PancTu-I cells retained by green tea catechin was attributed to the antioxidant effect in interference of the cancer cell division cycle through mediating the cytokines in modulation of cell cycle regulatory proteins, such as cyclins(37), a cell division regulators, cyclin-dependent kinase (Cdk) enzymes(37) activated by cyclins(37) in regulated cell progression through cell cycle arrest, and CDK inhibitors(37) with function in prevented over proliferation of cancer cells.
All 3 components of green tea catechins also demonstrated a substantiated effect in ameliorated secretion of pro-inflammatory and invasion promoting proteins of the cancer cell through expression of TNF tumor necrosis factor(37) in activated of the nuclear factor NF-κB protein signalling(37) involved mediation of DNA transcript, pro inflammatory cytokines production and cancer cell survival.
Tumor necrosis factor is a cell-signaling protein possessed a wide range of proinflammatory actions
NF-κB is a protein with function in controlled transcription of DNA, cytokine production and cell survival.
Once again, green tea catechins ECG and CG exhibit potent and much stronger anti-proliferate and anti-inflammatory activities on PDAC cells(37) in compared to EGCG
In human pancreatic cancer cells lines MIA PaCa-2 cells, injection of green tea EGCG plus Bleomycin, (BLM), an anti-cancer chemotherapeutic drug displayed a substantial effect in inhibited cell proliferation through cell cycle transition phase arrest and mitochondrial depolarization by mitochondrial permeability transition in induction of cell apoptosis, after 72 hours(38).
EGCG and BLM exhibited anti-proliferative effects significantly in induced apoptosis of MIA PaCa-2 cells(38) and suggested that this combination could represent a new strategy with potential advantages for treatment of pancreatic cancer.
In pancreatic cancer cell lines MIA PaCa-2 and PANC-1, injection of pterostilbene isolated from blue berry and EGCG expressed a strongly additive antiproliferative effect after 72 hours with MIA(39) underwent S-phase arrest but not in cancer cell line PANC-1(39).
Both pterostilbene and EGCG induced mitochondrial depolarization in enhanced cytochrome c released from mitochondria(39) to trigger programmed cell death during the early stages of apoptosis was observed also in MIA, but not in PANC
EGCG increased caspase-3/7 function in induced cell apoptosis in MIA(39) but the combined treatment did not significantly increase the activity in either cell lines.(39) these contradictory activities may indicate that cell death occurs in MIA, possibly through another mechanism.
15. Kidney Cancer
According to statistic, kidney cancer is very uncommon in people younger than age 45 and among the 10 most common cancers in both gender.
In 250 newly diagnosed, histo-logically confirmed Clear cell renal cell carcinoma (CCRCC) cases and 299 sex-, age-matched healthy controls provided complete information by face-to-face interview in Shanghai between 2007 and 2009, application of green tea at dose of ≥500 ml/d demonstrated a significantly inverse association to risk of CCRCC(40).
Green tea consumption of lower than the said volume such as 8 oz (237 ml) or more cups/day was also associated to decrease renal cell cancer risk, in compared to non drinkers, according to the report of Brigham and Women's Hospital and Harvard Medical School.
CCRCC risk induced by interaction with the environmental exposures association to polymorphisms of the xenobiotic-metabolizing enzymes also inhibited by green tea extract through increasing serum and liver antioxidant capacity and strengthening stability of microsomal and lysosomal membranes of healthy cells in compared to control(41).
In free radical aspect, the examine Wistar rats induced renal cancer pre-treated with N-ethyl-N-hydroxyethylnitrosamine (EHEN) by oral injection of drinking water for 2 weeks, also found that administration of green tea extract catechin ( 0.1% polyphenon-60) over 30 weeks of period of treatment exhibits a significant effect in decreased the incidence of renal cell tumors greater than 3 mm in diameter(42) but not tumors that are less than 3 mm in diameter942), through over expression of antioxidant in suppression of reactive oxygen species (ROS) induced by N-ethyl-N-hydroxyethylnitrosamine (EHEN) pre-treatment(42).
In alternated gene expression increased prevalence of cancer in human subjects, application of green tea polyphenol, catechins reverse change of DNA methylation in contributed to the tumor repressive gene of RGS2 (regulator of G-protein signaling 2) in modulated expression of cancers and increased the regulation of conversion of DNA to RNA (transcription) of these genes(43) in ameliorated risk of renal and other cancer(s).
Combined application of of green tea extract bioactive catechins and epigallocatechin gallate also showed to modulate DNA methylation by attenuating the effect of DNA methyltransferase 1 (DNMT1)(43) to ensure the fidelity of replication of inherited epigenetic patterns.
Aberrant DNA methylation patterns are associated with increased prevalence of renal and other tumor(s).
16. Skin Cancer
According to statistic, approximately, 87,110 new cases of invasive melanoma are diagnosed in the U.S every years
The evaluation of green tea effect in overexposure to environmental solar ultraviolet (UV) radiation (290-400 nm) which has been found to increase risk of the development of melanoma and non-melanoma skin cancers in mice model showed that oral administration of green tea pylophenols (GTPs) in drinking water or the topical application of EGCG prevents UVB-induced skin tumor development in tested subjects(44).
(-)-Epigallocatechin-3-gallate (EGCG), the major and most photoprotective polyphenolic component of green tea exhibited a protective activity against UV in induction of skin cancer(44), through induction of immunoregulatory cytokine interleukin (IL) 12 in differentiation of naive T cells into Th1 cells(44) and acted as T cell-stimulating factor in stimulate the growth and function of T cells.
Moreover, interleukin (IL) 12 also demonstrated a significant effect as an antagonist against immunosuppression induced by solar/ultraviolet (UV) radiation(44) by restoring immune responses and also stimulating DNA repair.
Green tea (-)-Epigallocatechin-3-gallate (EGCG) inhibited UV in induction of skin tumors; angiogenetic effect(45)in stimulated production of new blood vessels to provide nutrients and oxygen for cancer cells proliferation and survivals and initiated cytotoxic T lymphocyte cells in induced cancer and infectious and damage cells apoptosis.
Additional study of green tea polyphenols (GTPs) in prevention of UVB irradiated (80 mJ/cm(2)) 3 times each week for 24 wk in induced skin cancer in mice divided in to group consumed water and group fed with water containing 2 g/L GTPs, showed that group treated with GTPs displayed a significant reduced UVB-induced tumor incidence by 35%, tumor multiplicity by 63%, and tumor growth by 55% in compared to non treatment group(46).
Group treated with GTPs+UVB also demonstrated a reduced expression of the matrix metalloproteinases (MMP)-2 and MMP-9(46), which are activators associated with progression from benign to advanced cancer and expression of specific endogenous tissue inhibitors of metalloproteinases (TIMPs), tissues inhibitor of MMP in skin tumors in compared to mice treated with UVB alone.
GTPs+UVB group also reduced expressions of CD31 and vascular endothelial growth factor(46), in activated development of new blood vessel to nourish skin tumor cells proliferation and site expansion and inhibited expression of proliferating cell nuclear antigen, a key factor in DNA replication and cell cycle regulation in skin cancer in compared to UVB group.
Mice treated with GTPs+UVB group also showed more cytotoxic CD8(+) T cells in the tumors in compared to UVB group(46) by exhibited greater activation of caspase-3 epression in induced apoptosis of the tumor cells.
17. Oral Cancer
According to statistic, 1 in 75 men and 1 in 150 women will be diagnosed with oral cancer during their lifetime.
In human oral squamous carcinoma cells (SCC-25, SCC-9), application of green tea catechin, (-)-epigallocatechin-3-gallate (EGCG) suppressed SIRT3 mRNA(47) and protein expression in induction of SCC-25 cells proliferation(47), through antioxidant effect in attenuated function of SIRT3 in contribution to cancer cell survival via mRNA transmitting by modulating oxidative stress..
Some reserachers also insisted that SIRT 3 may be considered as a bio-maker for targeting stage and grade of cancer progression.
Green tea bioactive EGCG also up regulated the nuclear localization of the estrogen-related receptor α (ERRα)(47) in inhibited oral cell carcinoma tumors by regulating SIRT3(47) in expression of cancer cellular metabolism.
EGCG application displayed a significant effect in modulated the mRNA expressions of SIRT3-associated to cancer cell in induction of cell proliferation through inhibiting the production of reactive oxidative species in precipitated chain reactive in initiation of cancer cell division.
In ROS perspective, oral administration of green tea EGCG by targeting the protein SIRT3(48) in exhibited antioxidant effect in protect healthy cells without affecting formation of ROS to facilitate oral cancer cell apoptosis through cytotoxicity(48).
Dr. Tao L(48), after taking into account of other cofounders, said, "SIRT3 represents a novel potential target through which EGCG exerts differential prooxidant effects in cancer and normal cells".
EGCG treatment increased the production of mitochondrial H2O2 in SCC-25 cells(48) within 6 hours before inducing cancer cells apoptosis.
In antioxidant activity. green extract EGCG induced differential expression of genes related to antioxidant defense in oral cancer cell and gingival fibroblasts(48), which are critical in sustaining inflammation in periodontal disease through ameliorated expression of metallothionein 3 in induction of degeneration of cells and superoxide dismutase 2/3, and thioredoxin reductase 2(48) in facilitate oxidative stress to induce oncogenesis without increased cell proliferation of human gingival fibroblast -1 (HGF-1)(48).
Additional examination indicated that the application also exhibited anti oral cancer apoptosis by increased expression of mitochondrial ROS(48) and mitochondrial dysfunction(48) in facilitated intoxicate effect without causing harm to the gingival fibroblasts through antioxidant selective activities.
Green tea with promising chemo properties due to their decreased dose and limited toxicity profiles, Dr. Ramshankar V(49), the lead author said, "It is worthwhile to include green tea extract in an oral screening program for evaluating the pre-malignant lesions comparing the results between the treated and untreated group. Given the wide acceptance of green tea, its benefits may help in effective chemo-prevention oral cancer".
Summary
Taken together, the information findings suggested that green tea and its bioactive polyphenols such as catechin, (-)-epigallocatechin-3-gallate (EGCG) may have a profound and therapeutic effect in reduced risk of various types of cancer, however, due to limitation of this review, further research and studies are necessary before green tea can be recommended as a functional food in prevented risk and adjunct therapy for treatment of cancers.
Author Biography
Kyle J. Norton (All right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.
Sources
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(3) Green Tea Catechin, EGCG, Suppresses PCB 102-Induced Proliferation in Estrogen-Sensitive Breast Cancer Cells by Baker KM1, Bauer AC2.(PubMed)(4) Preparation of catechin extracts and nanoemulsions from green tea leaf waste and their inhibition effect on prostate cancer cell PC-3 by Tsai YJ1, Chen BH1.(PubMed)
(5)Reduced prostate cancer risk with green tea and epigallocatechin 3-gallate intake among Hong Kong Chinese men by Lee PMY1, Ng CF2, Liu ZM3, Ho WM4, Lee MK5, Wang F1, Kan HD6, He YH7, Ng SSM2, Wong SYS1, Tse LA1.(PubMed)
(6) Green tea and the risk of prostate cancer: A systematic review and meta-analysis by Guo Y1, Zhi F, Chen P, Zhao K, Xiang H, Mao Q, Wang X, Zhang X.(PubMed)
(7) Overexpression of miR-126 sensitizes osteosarcoma cells to apoptosis induced by epigallocatechin-3-gallate by Jiang L, Tao C, He A, He X1.(PubMed)
(8) Green tea polyphenol EGCG suppresses osteosarcoma cell growth through upregulating miR-1 by Zhu K1, Wang W2.(PubMed)
(9) Tumoricidal effects of a selenium (Se)-polysaccharide from Ziyang green tea on human osteosarcoma U-2 OS cells by Wang Y1, Chen J, Zhang D, Zhang Y, Wen Y, Li L, Zheng L.(PubMed)(10) Green tea catechin, epigallocatechin-3-gallate, attenuates the cell viability of human non-small-cell lung cancer A549 cells via reducing Bcl-xL expression by Sonoda JI1, Ikeda R2, Baba Y3, Narumi K1, Kawachi A1, Tomishige E1, Nishihara K1, Takeda Y2, Yamada K4, Sato K5, Motoya T1.(PubMed)
(11) Gene regulation mediated by microRNAs in response to green tea polyphenol EGCG in mouse lung cancer by Zhou H, Chen JX, Yang CS, Yang MQ, Deng Y, Wang H.(PubMed)
(12) Green tea extract induces protective autophagy in A549 non-small lung cancer cell line by Izdebska M1, Klimaszewska-Wiśniewska A1, Hałas M1, Gagat M1, Grzanka A1.(PubMed)
(13) Hyaluronic acid-green tea catechin micellar nanocomplexes: Fail-safe cisplatin nanomedicine for the treatment of ovarian cancer without off-target toxicity by Bae KH1, Tan S1, Yamashita A1, Ang WX1, Gao SJ1, Wang S1, Chung JE1, Kurisawa M2.(PubMed)
(14) Epigallocatechin-3-gallate delivers hydrogen peroxide to induce death of ovarian cancer cells and enhances their cisplatin susceptibility by Chan MM1, Soprano KJ, Weinstein K, Fong D.(PubMed)
(15) Anticancer effects of (-)-epigallocatechin-3-gallate on ovarian carcinoma cell lines by Huh SW1, Bae SM, Kim YW, Lee JM, Namkoong SE, Lee IP, Kim SH, Kim CK, Ahn WS.(PubMed)(16) Epigallocatechin-3-gallate(EGCG) suppresses melanoma cell growth and metastasis by targeting TRAF6 activity by Zhang J1,2, Lei Z1,2, Huang Z3, Zhang X1,2, Zhou Y1,2, Luo Z1,2, Zeng W1,2, Su J1,2, Peng C1,2, Chen X1,2.(PubMed)
(17) EGCG enhances TRAIL-mediated apoptosis in human melanoma A375 cell line by Shen Q1, Tian F, Jiang P, Li Y, Zhang L, Lu J, Li J.(PubMed)
(18) Epigallocatechin-3-O-gallate up-regulates microRNA-let-7b expression by activating 67-kDa laminin receptor signaling in melanoma cells by Yamada S1, Tsukamoto S1, Huang Y1, Makio A1, Kumazoe M1, Yamashita S1, Tachibana H1.(PubMed)
(19) Tea polyphenols EGCG and TF restrict tongue and liver carcinogenesis simultaneously induced by N-nitrosodiethylamine in mice by Sur S1, Pal D2, Roy R2, Barua A2, Roy A3, Saha P2, Panda CK4.(PubMed)
(20) Tea polyphenols epigallocatechin gallete and theaflavin restrict mouse liver carcinogenesis through modulation of self-renewal Wnt and hedgehog pathways by Sur S1, Pal D2, Mandal S3, Roy A4, Panda CK5.(PubMed)(21) (-)-Epigallocatechin-3-gallate inhibits VEGF expression induced by IL-6 via Stat3 in gastric cancer by Zhu BH1, Chen HY, Zhan WH, Wang CY, Cai SR, Wang Z, Zhang CH, He YL.(PubMed)
(22) [(-)-Epigallocatechin-3-gallate reduces vascular endothelial growth factor expression in gastric cancer cells via suppressing activity].[Article in Chinese] by Zhu BH1, He YL, Zhan WH, Cai SR, Wang Z, Zhang CH, Chen HY.(PubMed)
(23) Reversal of 5-fluorouracil resistance by EGCG is mediate by inactivation of TFAP2A/VEGF signaling pathway and down-regulation of MDR-1 and P-gp expression in gastric cancer by Tang H1,2, Zeng L2, Wang J2, Zhang X2, Ruan Q2, Wang J2, Cui S2, Yang D1.(PubMed)
(24) Apoptotic effect of EGCG in HT-29 colon cancer cells via AMPK signal pathway by Hwang JT1, Ha J, Park IJ, Lee SK, Baik HW, Kim YM, Park OJ.(PubMed)
(25) Reduction in promotor methylation utilizing EGCG (epigallocatechin-3-gallate) restores RXRα expression in human colon cancer cells by Morris J1, Moseley VR2, Cabang AB1, Coleman K2, Wei W3, Garrett-Mayer E4, Wargovich MJ1.(PubMed)(26) Immunomodulatory effect of tea saponin in immune T-cells and T-lymphoma cells via regulation of Th1, Th2 immune response and MAPK/ERK2 signaling pathway by Bhardwaj J1, Chaudhary N, Seo HJ, Kim MY, Shin TS, Kim JD.(PubMed)
(27) Inhibition of angiogenesis and induction of endothelial and tumor cell apoptosis by green tea in animal models of human high-grade non-Hodgkin's lymphoma by Bertolini F1, Fusetti L, Rabascio C, Cinieri S, Martinelli G, Pruneri G.(PubMed)
(28) Green tea, black tea consumption and risk of endometrial cancer: a systematic review and meta-analysis by Zhou Q1, Li H2, Zhou JG3, Ma Y4, Wu T5, Ma H6.(PubMed)
(29) A prodrug of green tea polyphenol (-)-epigallocatechin-3-gallate (Pro-EGCG) serves as a novel angiogenesis inhibitor in endometrial cancer by Wang J1, Man GCW2, Chan TH3, Kwong J1, Wang CC4.(PubMed)
(30) (-)-Epigallocatechin-3-gallate induces apoptosis in human endometrial adenocarcinoma cells via ROS generation and p38 MAP kinase activation by Manohar M1, Fatima I, Saxena R, Chandra V, Sankhwar PL, Dwivedi A.(PubMed)
(31) Epigallocatechin-3-gallate promotes apoptosis and reversal of multidrug resistance in esophageal cancer cells by Liu L1, Ju Y2, Wang J3, Zhou R3.(PubMed)
(32) Epigallocatechin-3-gallate suppresses cell proliferation and promotes apoptosis in Ec9706 and Eca109 esophageal carcinoma cells by Liu L1, Zuo J1, Wang G1.(PubMed)
(33) Epigallocatechin-3-gallate inhibits growth and induces apoptosis in esophageal cancer cells through the demethylation and reactivation of the p16 gene by Meng J1, Tong Q2, Liu X2, Yu Z3, Zhang J3, Gao B3.(PubMed)(34) A component of green tea, (-)-epigallocatechin-3-gallate, promotes apoptosis in T24 human bladder cancer cells via modulation of the PI3K/Akt pathway and Bcl-2 family proteins by Qin J1, Xie LP, Zheng XY, Wang YB, Bai Y, Shen HF, Li LC, Dahiya R.(PubMed)
(35) The treatment of bladder cancer in a mouse model by epigallocatechin-3-gallate-gold nanoparticles by Hsieh DS1, Wang H, Tan SW, Huang YH, Tsai CY, Yeh MK, Wu CJ.(PubMed)
(36) Green tea polyphenol suppresses tumor invasion and angiogenesis in N-butyl-(-4-hydroxybutyl) nitrosamine-induced bladder cancer by Sagara Y1, Miyata Y, Nomata K, Hayashi T, Kanetake H.(PubMed)
(37) Epicatechin gallate and catechin gallate are superior to epigallocatechin gallate in growth suppression and anti-inflammatory activities in pancreatic tumor cells. by Kürbitz C1, Heise D, Redmer T, Goumas F, Arlt A, Lemke J, Rimbach G, Kalthoff H, Trauzold A.(PubMed)
(38) Inhibitory effect of (-)-epigallocatechin-3-gallate and bleomycin on human pancreatic cancerMiaPaca-2 cell growth by Bimonte S#1, Leongito M#1, Barbieri A2, Del Vecchio V2, Barbieri M1, Albino V1, Piccirillo M1, Amore A1, Di Giacomo R1, Nasto A1, Granata V3, Petrillo A3, Arra C2, Izzo F1.(PubMed)
(39) Inhibitory effects of (-)-epigallocatechin-3-gallate and pterostilbene on pancreatic cancer growth in vitro by Kostin SF1, McDonald DE, McFadden DW.(PubMed)(40) Risk factor for clear cell renal cell carcinoma in Chinese population: a case-control study by Wang G1, Hou J, Ma L, Xie J, Yin J, Xu D, Chang W, Tan X, Su T, Zhang H, Cao G.(PubMed)
(41) [Effects of green tea extract and its components on antioxidant status and activities of xenobiotic metabolizing enzymes of rats] by [Article in Russian](PubMed)
Kravchenko LV, Trusov NV, Aksenov IV, Avren'eva LI, Guseva GV, Lashneva NV, Tutel'ian VA.
(42) Effect of polyphenon-60 on the development of renal cell tumors in rats treated with N-ethyl-N hydroxyethylnitrosamine byYoshioka N1, Hiasa Y, Cho M, Kitahori Y, Hirao K, Konishi N, Kuwashima S.(PubMed)
(43) Targeting DNA Methylation with Green Tea Catechins by Yiannakopoulou E.C.(Karger)
(44) Green Tea Prevents Skin Cancer by Two Mechanisms by Navid Bouzari, Yvonne Romagosa, Robert S. Kirsner(PubMed)
(45) Green tea and skin cancer: photoimmunology, angiogenesis and DNA repair by Katiyar S1, Elmets CA, Katiyar SK.(PubMed)
(46) Orally administered green tea polyphenols prevent ultraviolet radiation-induced skin cancer in mice through activation of cytotoxic T cells and inhibition of angiogenesis in tumors by Mantena SK1, Meeran SM, Elmets CA, Katiyar SK.(PubMed)(47) Differential prooxidative effects of the green tea polyphenol, (-)-epigallocatechin-3-gallate, in normal and oral cancer cells are related to differences in sirtuin 3 signaling by Tao L1, Park JY, Lambert JD.(PubMed)
(48) The role of the mitochondrial oxidative stress in the cytotoxic effects of the green tea catechin, (-)-epigallocatechin-3-gallate, in oral cells.by Tao L1, Forester SC, Lambert JD.(PubMed)
(49) Chemoprevention of oral cancer: Green tea experience by Ramshankar V1, Krishnamurthy A2.(PubMed)
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