Friday, April 25, 2014

Cervical cancer in Vitamin K Points of View

Kyle J. Norton(Draft Article)

According to the American Cancer Society's, in 2014, 12,360 new cases of invasive cervical cancer will be diagnosed with the death of  4,020 patients. The risk of cervical cancer is higher in Hispanic women followed by African-Americans, Asians and Pacific Islanders, and whites(1).
Vitamin K(K1, phylloquinone; K2, menaquinones), is a fat soluble vitamin, found abundantly in leafy green vegetables, broccoli, and Brussels sprouts, etc. It is best known for promotion of coagulation and bone health.

Vitamin K3 (2-methyl-1,4-naphthoquinone), also known as menadione, found effectively in inhibition of the profileration of human cervical epithelial cancer cells (HeLa), through binding of tubulin, a small family of globular proteins, including α-tubulin and β-tubulin posible with function of cell division and the movement of materials within cells(1)(2). Other synthetic vitamin K analogue, 2-(2-mercaptoethanol)-3-methyl-1,4-naphthoquinone or compound 5 (Cpd 5) found effectively inhibited tumors through arrested cell cycle progression at both G1 and G2-M(3). In cervical carcinoma SiHa cells, Vitamin K3 (VK3)exerted its anti proliferative effects through inhibited cyclin expression via cell cycle arrest and transition of the aphidicolin-synchronised SiHa cells(4)and induced cytotoxicity in human cervical-carcinoma tsgh8302 cells, through exhibited chromatin condensation and DNA fragmentation(5).

Taking altogether, synthetic Vitamin K and its analogue have shown to reduced risk of and treatment of cervical cancer through cell cycle arrest and regulation of cancer cell proliferation. Further studies with large sample size and multi center studies to validate the effectiveness are necessary. Overdoses can induce symptoms of Skin rash,  Diarrhea, Nausea, Vomiting, Anemia, etc. Please make sure you follow the guideline of the Institute of Medicine of the National Academies.

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References
(1)Vitamin K3 disrupts the microtubule networks by binding to tubulin: a novel mechanism of its antiproliferative activity by Acharya BR1, Choudhury D, Das A, Chakrabarti G.(PubMed)
(2) Mystery of Vital Cell Protein Solved After 30 Years. Receive News Releases Immediately Via E-mail By Lynn Yarris, lcyarris@lbl.gov (Berkeley Lab)
(3) Cdc25 inhibition and cell cycle arrest by a synthetic thioalkyl vitamin K analogue by Tamura K1, Southwick EC, Kerns J, Rosi K, Carr BI, Wilcox C, Lazo JS.(PubMed)

(3) Vitamin K3 induces cell cycle arrest and cell death by inhibiting Cdc25 phosphatase by Wu FY1, Sun TP.(PubMed)
(4) Vitamin-k-3 induces cell-death via apoptosis in human cervical-carcinoma tsgh8302 cells by Wu F, Chang W, Sun T.(PubMed)

 

Thursday, April 24, 2014

Cervical cancer in Vitamin E Points of View

 Kyle J. Norton(Draft Article)

According to the American Cancer Society's, in 2014, 12,360 new cases of invasive cervical cancer will be diagnosed with the death of  4,020 patients. The risk of cervical cancer is higher in Hispanic women followed by African-Americans, Asians and Pacific Islanders, and whites(1).
Epidemiological studies, linking vitamin E in reduced risk of cervical cancer have not been consistent(1a)(1b)(1c)(1d), but no doubt of its effectiveness in improvement of quality of life, through reduction of oxidative stress(2)(2a)

Vitamin E,  a fat soluble vitamin, consisting eight different variants (alpha-, beta-, gamma-, and delta-tocopherol and alpha-, beta-, gamma-, and delta-tocotrienol) with varying levels of biological activity(3), found abundantly in corn oil, soybean oil, margarine, wheat germ oil, sunflower,safflower oils, etc. plays an important role in neurological functions and inhibition of platelet aggregation, regulation of enzymatic activity, free radical scavenger, etc..

The Universidad Autónoma de Ciudad Juarez study indicated the effectiveness of  dietary supplements, including vitamin E are associated to reduced risk of cervical cancer but depending to the specific factors of the diseases(4)(5). The study from 1National Cancer Center, of Korea, showed a strong inverse effect of antioxidants vitamin E against risk of cervical cancer in a 144 cervical cancer cases and 288 age-matched, hospital-based controls using unconditional logistic regression models(6). Tocotrienols, variants of vitamin E, including alpha-, beta-, gamma-, and delta-  of palm oil in the testing against human cervical cancer cell line showed a strong effects of alphaT3 and gammaT3  induced cell death.through cell cycle arrest at G2/M phase and triggered apoptosis in  a dose-dependent and time-dependent manner(7).
The Vilnius University study in the assessing the parameters of immune and antioxidant systems in patients with cervical cancer indicated a lower levels of antioxidant vitamin E and the activity of the antioxidant enzyme superoxide dismutase in comparison with the control group(8)(8a). Oral administration of alpha-tocopherol and quercetin, exerted their antioxidants effects in protection of  DNA damage against free radicals through detoxification by increased glutathione and glutathione-s-transferase (9). The study at the University of Colorado Health Sciences Center of three human cancer cell lines, including cervical cancer (HeLa), indicated that d-alpha-tocopheryl succinate (alpha-TS)  induced chromosomal damage in both human cervical cancer cells and ovarian cancer cells, but not in human normal fibroblasts in culture and enhanced the level of radiation-induced chromosomal damage in cancer cells, but it protected normal cells against such damage(10).

Taking altogether, without going into reviews, Vitamin E and its variants may have a protective effect in reduced risk of cervical cancer through its antioxidant properties. But further studies with large sample sizes and multi centers studies are necessary to validate its claims. Over doses of vitamin E supplement can cause symptoms of blurred vision, weakness, dizziness, nausea, diarrhea, etc., please make sure you follow the guideline of the Institute of Medicine of the National Academies.

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References
(1) Cerical cancer (Amerrican cancer society)
(1a) Dietary intakes of selected nutrients and food groups and risk of cervical cancer by Ghosh C1, Baker JA, Moysich KB, Rivera R, Brasure JR, McCann SE.(PubMed)
(1b) Intakes of selected nutrients and food groups and risk of ovarian cancer by McCann SE1, Moysich KB, Mettlin C.(PubMed)
(1c) Food consumption pattern in cervical carcinoma patients and controls by Labani L1, Andallu B, Meera M, Asthana S, Satyanarayana L.(PubMed)
(1d) A case-control study of nutrient status and invasive cervical cancer. I. Dietary indicators by Herrero R1, Potischman N, Brinton LA, Reeves WC, Brenes MM, Tenorio F, de Britton RC, Gaitan E.(PubMed)
(2)[Effect of antioxidant supplementation over oxidative stress and quality of life in cervical cancer].
[Article in Spanish] by Fuchs-Tarlovsky V1, Bejarano-Rosales M, Gutiérrez-Salmeán G, Casillas MA, López-Alvarenga JC, Ceballos-Reyes GM (PubMed)
(2a) Alpha-tocopherol and alpha-tocopheryl quinone levels in cervical intraepithelial neoplasia and cervical cancer by Palan PR1, Woodall AL, Anderson PS, Mikhail MS.(PubMed)
(3) Traber MG. Vitamin E. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins R, eds. Modern Nutrition in Health and Disease. 10th ed. Baltimore, MD: Lippincott Williams & Wilkins, 2006;396-411.
(4) [Dietary supplements as a treatment for cervical cancer: a systematic review].
[Article in Spanish] by Arellano Ortiz AL1, Jiménez Vega F1, Salcedo Vargas M2.(PubMed)
(5) Vitamin or antioxidant intake (or serum level) and risk of cervical neoplasm: a meta-analysis by Myung SK1, Ju W, Kim SC, Kim H; Korean Meta-analysis (KORMA) Study Group.(PubMed)
(6) Intakes of vitamin A, C, and E, and beta-carotene are associated with risk of cervical cancer: a case-control study in Korea by Kim J1, Kim MK, Lee JK, Kim JH, Son SK, Song ES, Lee KB, Lee JP, Lee JM, Yun YM.(PubMed)
(7) Tocotrienols inhibited growth and induced apoptosis in human HeLa cells through the cell cycle signaling pathway by Wu SJ1, Ng LT.(PubMed)
(8) [Changes in the parameters of immune and antioxidant systems in patients with cervical cancer].
[Article in Lithuanian] by Kazbariene B1, Prasmickiene G, Krikstaponiene A, Sukeliene D, Burneckis A, Didziapetriene J.(PubMed)
(8a) Plasma concentrations of coenzyme Q10 and tocopherols in cervical intraepithelial neoplasia and cervical cancer by Palan PR1, Mikhail MS, Shaban DW, Romney SL.(PubMed)
(9) Comparative evaluation of cancer chemopreventive efficacy of alpha-tocopherol and quercetin in a murine model by De S1, Chakraborty RN, Ghosh S, Sengupta A, Das S.(PubMed)
(10) D-alpha-tocopheryl succinate (vitamin E) enhances radiation-induced chromosomal damage levels in human cancer cells, but reduces it in normal cells by Kumar B1, Jha MN, Cole WC, Bedford JS, Prasad KN.(PubMed)

Wednesday, April 23, 2014

Cervical cancer in Vitamin D Points of View


According to the American Cancer Society's, in 2014, 12,360 new cases of invasive cervical cancer will be diagnosed with the death of  4,020 patients. The risk of cervical cancer is higher in Hispanic women followed by African-Americans, Asians and Pacific Islanders, and whites(a).

Vitamin D is a fat-soluble secosteroids found in small amount in few foods, including salmon, mackerel, sardines and tuna. The vitamin plays an important role in modulation of cellular proliferation, apoptosis induction, tumor growth suppression and promotion in absorption of minerals, including calcium, iron, magnesium, phosphate and zinc.


The Medical Center Bonn Friedensplatz, study showed a preferential risk factor of cancer in patient with low levels of concentration of serum vitamin D, including cervix carcinoma(1). 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), a biologically active metabolite of vitamin D, showed to regulate the growth of various cell types. The expression of VDR, 25-OHase, 1alpha-OHase, and 24-OHase in breast carcinomas (BC), ovarian cancer (OC), cervix carcinomas (CC) might have the ability to synthesize 1alpha,25(OH)2D3 within the cells. Locally in regulating the proliferation and differentiation of the tissues(2). In the study of the same, 25(OH)D3-1alpha-hydroxylase have shown to express in normal cervical tissue, in cervical cancer and in HeLa cells. This local synthesization of 1alpha, 25(OH)2D3 may be of significant importance in the regulation of growth control in normal and malignant cervical tissue(3).
In human epithelioid carcinoma cells of cervix HeLa S3K, vitamins D3-induced alkaline phosphatase activity in malignant cells(4).
In a selected 405 incident cervical neoplasias (333 invasive carcinomas and 72 cervical intraepithelial neoplasias grade III (CIN3)) and 2025 age-matched non-cancer controls in Japanese women showed an inverse correction  between dietary calcium and vitamin D intake and cervical neoplasia risk(5).

Taking together, decreased serum of vitamin D might be associated to increased risk of  cervical cancer. Receptor of vitamin D and its active metabolite of vitamin D may be used to regulation of the cervical cancer tissues. Over doses of vitamin D supplement may cause excessive calcium absorption, calcification, Urinary stones etc. please make sure to follow the guideline of the Institute of Medicine of the National Academies.

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References
(1) Circulating 25-hydroxyvitamin D concentration in German cancer patients by Reinhold U1, Schmitz B, Kurbacher C, Nagel W, Schmidt M, Malaisse WJ.(PubMed)
(2) Analysis of the vitamin D system in cervical carcinomas, breast cancer and ovarian cancer by Friedrich M1, Rafi L, Mitschele T, Tilgen W, Schmidt W, Reichrath J.(PubMed)
(3) Analysis of 25-hydroxyvitamin D3-1alpha-hydroxylase in cervical tissue by Friedrich M1, Villena-Heinsen C, Axt-Fliedner R, Meyberg R, Tilgen W, Schmidt W, Reichrath J.(PubMed)
(4) Effect of vitamin D3 and 1,25(OH)2D3 on growth of neoplastically derived cell lines and their alkaline phosphatase activity by Kholodova YuD1, Bondar OP, Melnykovych G.(PubMed)

(5) Association between dietary calcium and vitamin D intake and cervical carcinogenesis among Japanese women by Hosono S1, Matsuo K, Kajiyama H, Hirose K, Suzuki T, Kawase T, Kidokoro K, Nakanishi T, Hamajima N, Kikkawa F, Tajima K, Tanaka H.(PubMed)

Food Therapy - Mushrooms(Agaricus bisporus)

Mushroom is a standard name of white button mushroom, the fleshy, spore-bearing fruiting body of a fungus produced above ground on soil or on its food source, It is a genus A. Muscaria and belong to the family Amanitaceae and has been cultivation in many cultures all over the world for foods and health benefits.
Nutrients1. Carbohydrates
2. Protein
3. Thiamine (Vitamin B1)
4. Riboflavin (Vitamin B2)
5. Niacin (Vitamin B3)
6. Pantothenic acid (Vitamin B5)
7. Calcium
8. Phosphorus
9. Potassium
10. Sodium
11. Selenium
12. Iron
13. Copper
14. Zinc
15. Etc.

Chemical constituents
Astraodorol, Psilocybin, Lectin, adustin, ribonuclease, nicotine, 2-hydroxy-4-methoxy-6-methylbenzoic acid, orsellinic acid, melleolide, ergosterol, genistein, daidzein, daucosterol, genistin, uracil and D-mannitol(a).


1. Button Mushroom and Ovarian cancer
Ovarian cancer is defined as a condition of abnormal cells growth of ovarian cells as that have become cancerous. It is one of most common cancer in US, according to the statistics adapted from the American Cancer Society's publication, Cancer Facts & Figures 2010, an estimated 21,880 women in the United States will be diagnosed with ovarian cancer and 13,850 deaths.
button mushrooms (Agaricus bisporus), in scientific literature suggests that dietary components may exert cancer preventive effects(1). According to the Curtin University and National Institute of Hygiene and Epidemiology, Hanoi, Vietnam, high levels of intake mushroom is associated to  reductions in cancer risk, especially in the incidence of epithelial ovarian cancer in southern Chinese women, in the study of 500 incident patients with epithelial ovarian cancer and 500 controls(2), But some researchers concerned that minerals of nutritional value are common constituents of mushrooms collected from natural habitats, the problem is however their co-occurrence with some hazardous elements including Cd, Pb, Hg, Ag, As, and radionuclides(3).


References
(a) [Chemical constituents from fungus Armillaria mellea]. by [Article in Chinese] by Yuan XL1, Yan LH, Zhang QW, Wang ZM.(PubMed)
(1) The cancer preventive effects of edible mushrooms by Xu T1, Beelman RB, Lambert JD.(PubMed)
(2) Mushroom intake and risk of epithelial ovarian cancer in southern Chinese women by Lee AH1, Pasalich M, Su D, Tang L, Tran VD, Binns CW.(PubMed)
(3) Macro and trace mineral constituents and radionuclides in mushrooms: health benefits and risks. by Falandysz J1, Borovička J.(PubMed)

2.  Button Mushroom and 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. In 2010, over 250,000 new cases of breast cancer were expected to be diagnosed in women in the U.S. alone and the risk of getting invasive breast cancer during life time of a women is 1/8.
Dietary intake of with button Mushroom  showed  to protect against breast cancer, but  little effect on the growth of human colon, prostate, gastric cancer, and murine Sarcoma 180 cells(1), may be through ROS-mediated mitochondrial apoptotic pathway(2)
In MCF-7 human breast cancer cells. extract from white button (WB, Agaricus bisporus) mushrooms or water alone (5% v/v), exerted its protective effect with significant suppression of  cellular proliferation(3).

References
(a) [Chemical constituents from fungus Armillaria mellea]. by [Article in Chinese] by Yuan XL1, Yan LH, Zhang QW, Wang ZM.(PubMed)
(1) Macrophage immunomodulating and antitumor activities of polysaccharides isolated from Agaricus bisporus white button mushrooms by Jeong SC1, Koyyalamudi SR, Jeong YT, Song CH, Pang G.(PubMed)
(2) ROS-dependent mitochondria molecular mechanisms underlying antitumor activity of Pleurotus abalonus acidic polysaccharides in human breast cancer MCF-7 cells by Shi X1, Zhao Y, Jiao Y, Shi T, Yang X.(PubMed)
(2) Commonly consumed and specialty dietary mushrooms reduce cellular proliferation in MCF-7 human breast cancer cells by Martin KR1, Brophy SK.(PubMed)

3. Button Mushroom and colon cancer
Bowel cancer also known as colorectal cancer, is defined as a condition of the abnormal proliferation of cells in the colon, rectum, or vermiform appendix. It is the third most commonly diagnosed cancer in developed countries, including US and Canada.
A. bisporus showed to inhibit colon cancer cell line through positively increased GPx-1 and GPx-2 gene expression and GPx-1 enzyme activity in rat colon, due to the presented selenium(1). the Methodist Research Institute, Indianapolis study showed a positive effect of A. bisporus in inhibition of colon cancer (HT-29, HCT-116) cells, through cell cycle arrest at G0/G1 phase(2) and reversibly inhibits cell proliferation occurred within 30 min of the lectin being bound to the cell surface(3).

References
(a) [Chemical constituents from fungus Armillaria mellea]. by [Article in Chinese] by Yuan XL1, Yan LH, Zhang QW, Wang ZM.(PubMed)
(1) Selenium-enriched Agaricus bisporus increases expression and activity of glutathione peroxidase-1 and expression of glutathione peroxidase-2 in rat colon by Maseko T1, Howell K, Dunshea FR, Ng K.(PubMed)
(2) Pleurotus ostreatus inhibits proliferation of human breast and colon cancer cells through p53-dependent as well as p53-independent pathway by Jedinak A1, Sliva D.(PubMed)
(3) Intracellular trafficking and release of intact edible mushroom lectin from HT29 human colon cancer cells Lu-Gang Yu1, David G. Fernig2 an Jonathan M. Rhodes (The Febs Journal)

4. Button mushroom and Cardiovascular disease (CVD)
Scientists may have found one of the natural food used in many different culture with a potential in reduced risk and protect against CVD.
Dietary fungi, such as, mushrooms, can protect against chronic disease by altering inflammatory environments through inhibition of inhibit cellular processes under pro-inflammatory conditions which are associated with CVD.
Strong evidences through epidemiological studies suggested that regular consumption of fruits and vegetables is strongly associated with a reduced risk of cardiovascular disease (CVD).
According to Dr. Martin KR., ergothioneine (ERT), a novel antioxidant, presented in edible mushrooms, accumulated through diet was found effective in interrupted pro-inflammatory induction of adhesion molecule expression associated with atherogenesis.
Mushroom, a standard name of white button mushroom, the fleshy, spore-bearing fruiting body of a fungus produced above ground on soil or on its food source, contains several important nutrients including Thiamine (Vitamin B1), Riboflavin (Vitamin B2), Niacin (Vitamin B3), Pantothenic acid (Vitamin B5),  Calcium, Phosphorus, Potassium, Sodium, Selenium, Iron, Copper and Zinc which are necessary to maintain the growth, body functions as well as protect against chronic diseases.
Its antioxidants such as Astraodorol, Psilocybin, Lectin, adustin, ribonuclease, nicotine, etc. may also consist the magic power in reduced risk and treatment of vary types of cancer, including colon, breast and gastric cancers through inhibition of cell cycle arrest, significant suppression of  cellular proliferation, n tested cancer cell lines.
These findings showed to support the notion of dietary mushrooms in protection of CVD, but multi canters and large sample size studies to identify the main ingredient which comparable to current medicine used are necessary to improve its validation.
But, the study of University of Gdańsk, in the reviews and updates data on macro and trace elements and radionuclides in edible wild-grown and cultivated mushrooms suggested that the coexistence of
minerals of nutritional value collected from natural habitats, and co-occurrence with some hazardous elements including Cd, Pb, Hg, Ag, As, and radionuclides should be taken certain precautions.



References
(1) The bioactive agent ergothioneine, a key component of dietary mushrooms, inhibits monocyte binding to endothelial cells characteristic of early cardiovascular disease by Martin KR.(PubMed)
(2) Both common and specialty mushrooms inhibit adhesion molecule expression and in vitro binding of monocytes to human aortic endothelial cells in a pro-inflammatory environment by Martin KR.(PubMed)
(3) Macro and trace mineral constituents and radionuclides in mushrooms: health benefits and risks. by Falandysz J1, Borovička J.(PubMed)
(4) Intracellular trafficking and release of intact edible mushroom lectin from HT29 human colon cancer cells Lu-Gang Yu1, David G. Fernig2 an Jonathan M. Rhodes (The Febs Journal)
(5) Commonly consumed and specialty dietary mushrooms reduce cellular proliferation in MCF-7 human breast cancer cells by Martin KR1, Brophy SK.(PubMed)
(6) Macro and trace mineral constituents and radionuclides in mushrooms: health benefits and risks. by Falandysz J1, Borovička J.(PubMed)
(7) Macro and trace mineral constituents and radionuclides in mushrooms: health benefits and risks.
(8) Fruit and vegetable consumption and all-cause, cancer and CVD mortality: analysis of Health Survey for England data by Oyebode O1, Gordon-Dseagu V, Walker A, Mindell JS.(PubMed)
(9) Seasonal consumption of salad vegetables and fresh fruit in relation to the development of cardiovascular disease and cancer by Cox BD1, Whichelow MJ, Prevost AT.(PubMed)
(10) Intakes of fruits, vegetables and carbohydrate and the risk of CVD by Joshipura KJ1, Hung HC, Li TY, Hu FB, Rimm EB, Stampfer MJ, Colditz G, Willett WC.(PubMed)


5. Button mushroom and Prostate cancer
Prostate cancer is defined as a condition in which the cells of prostate has become cancerous, causing abnormal cell growth which spread to the distant parts of the body. Most prostate cancers are slow growing and enlarged prostate and prostate cancer may be detected during the Physical (rectum) exams(1).
In athymic mice, conjugated linoleic acid (CLA), found in white button mushroom extract and its major component showed to inhibit proliferation in the prostate cancer cell lines in vitro within 72 hours and to decrease the prostate tumor size of DU145 and PC3(2). But according to the study by University of Western Sydney, Agaricus bisporus white button mushroom (WBM), in a tetrazolium dye [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]-based assay, it showed a little effect on the growth of human colon, prostate, gastric cancer, and murine Sarcoma 180 cells but breast cancer cell line MCF-7(3). Button mushrooms with a rich source of vitamin D2 that when consumed can increase and maintain blood levels of 25-hydroxyvitamin D in a healthy range(4) of that may lead to reduced risk of prostate cancer(5).

References
(1) Prostate Cancer (Health tips for better living and living health)
(2) White button mushroom (Agaricus bisporus) exhibits antiproliferative and proapoptotic properties and inhibits prostate tumor growth in athymic mice by Adams LS1, Phung S, Wu X, Ki L, Chen S.(PubMed)
(3) Macrophage immunomodulating and antitumor activities of polysaccharides isolated from Agaricus bisporus white button mushrooms by Jeong SC1, Koyyalamudi SR, Jeong YT, Song CH, Pang G.(PubMed)
(4)  Photobiology of vitamin D in mushrooms and its bioavailability in humans by Keegan RJ, Lu Z, Bogusz JM, Williams JE, Holick MF.(PubMed)
(5) Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland) by Merja H. Ahonen, Leena Tenkanen, Lyly Teppo, Matti Hakama, Pentti Tuohimaa (Springer link)

6. Button Mushroom and Immunologic effects
The immune system is the set of cells and their activity against antigens or infectious agents that comprises of the body's defense system against diseases. The immune system does a great job of keeping people healthy and preventing infections. Beside foods and nutritional supplements, herbs also play a important role in helping the immune system defend against viruses and bacteria attacks.
In number of studies, Mushrooms have been shown to enhance immune response. according to Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, white button mushroom showed to enhance both innate and T cell-mediated immunity leading to a more efficient surveillance and defense mechanism against microbial invasion and tumor development, through promotion of DC maturation and enhance their antigen-presenting function.(1). A. bisporus polysaccharides isolated from white button mushrooms, exhibited macrophage immunomodulating and antitumor activities, through stimulation the production of nitric oxide, interleukin-6, and tumor necrosis factor-α via activation of nuclear factor-κB with the production p50/105 heterodimers(2).

References
(1) White button mushroom enhances maturation of bone marrow-derived dendritic cells and their antigen presenting function in mice by Ren Z1, Guo Z, Meydani SN, Wu D.(PubMed)
(2) Macrophage immunomodulating and antitumor activities of polysaccharides isolated from Agaricus bisporus white button mushrooms by Jeong SC1, Koyyalamudi SR, Jeong YT, Song CH, Pang G(PubMed)

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7. Button mushroom and Anti-inflammatory activities
Chronic inflammatory processes contribute to the pathogenesis of many age-related diseases. Button mushroom showed to retain anti-inflammatory activities even after 'cooking', allowing its active compounds to reach therapeutic levels in target tissues, through inhibited NO production, according to selection of 115 samples prepared by a generic food-compatible processing method involving heating by University of Western Sydney(1). Ethanolic extract of white button mushroom, also showed a significantly enhanced the activities of antioxidant enzymes in serums, livers and hearts of administration of mice, in vitro and vivo(2).

References
(1) Determination of anti-inflammatory activities of standardised preparations of plant- and mushroom-based foods by Gunawardena D1, Shanmugam K, Low M, Bennett L, Govindaraghavan S, Head R, Ooi L, Münch G.(PubMed)
(2) In vitro and in vivo antioxidant activity of ethanolic extract of white button mushroom (Agaricus bisporus) by Liu J1, Jia L, Kan J, Jin CH.(PubMed)


8.  Button mushroom and Hepatic Steatosis
Cholesterol is needed for our body to build cell walls, make hormones and vitamin D, and create bile salts that help you digest fat. However too much of it can be dangerous because cholesterol cannot dissolve in your blood. The special particle called lipoprotein moves this waxy, soft substance from place to place.
Hepatic Steatosis is the early stage of Non-alcoholic Fatty Liver Disease which is defined as a condition of the fatty liver diseases as a result of accumulated of fat in the liver, not caused by abusive alcohol consumption.
In HepG2 cell line, button mushroom (WBM), Agaricus Bisporus, has protective effects against liver steatosis in ovariectomized (OVX) mice, though down regulating genes related to the fatty acid biosynthesis pathway, particularly for fatty acid synthetase (Fas) and fatty acid elongase 6 (Elovl6)(1).

References
(1) Protective effects of white button mushroom (Agaricus bisporus) against hepatic steatosis in ovariectomized mice as a model of postmenopausal women by Kanaya N1, Kubo M, Liu Z, Chu P, Wang C, Yuan YC, Chen S.(PubMed)


9. Button mushroom and Arthritis
Arthritis is a condition of inflammation of one or more joints
According to Oklahoma State University, white button mushroom in the  reduce the incidence and severity of collagen-induced arthritis(CIA) in dilute brown non-agouti mice, through deduction of reduce the CIA index and plasma TNFα(1).
References
(1) White button and shiitake mushrooms reduce the incidence and severity of collagen-induced arthritis in dilute brown non-agouti mice by Chandra L1, Alexander H, Traoré D, Lucas EA, Clarke SL, Smith BJ, Lightfoot SA, Kuvibidila S.(PubMed)

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Tuesday, April 22, 2014

Cervical cancer in Vitamin C Points of View

 Kyle J. Norton(Draft Article)

Vitamin C, also known as L-ascorbic acid, is a water-soluble vitamin, found in fresh fruits, berries and green vegetables. It is best known for its free radical scavengers activity and regenerating oxidized vitamin E for immune support.
Epidemiological studies linking vitamin C in reduced risk of cervical cancer may be inconclusive(1)(1c)(1a)(1b), but no doubt in acceptance of improved quality of life(QoL)(2).

D-Glucopyranosyl-L-ascorbic acid (AA-2βG), a novel stable vitamin C analog isolated from Lycium barbarum fruit induced Hela cell apoptosis through cell cycle arrest(3). A  case-control study including 239 cases diagnosed with squamous cell carcinoma of the cervix and 979 hospital patients with nonneoplastic found a significant reductions in risk of approximately 40-60% observed for women in the highest vs. lowest tertiles of dietary intake, including vitanin C(4)(4a). In human cervical cancer CaCx patients of the age group of 25-65 years, oral administration of vitamin C reduced oxidative stress risk of CaCx with no side effect(5). A nutrient mixture (NM) containing lysine, proline, arginine, ascorbic acid, and green tea extract inhibited 100% of invasion of human cervical cancer cells CCL-2 and DoTc2 4510 at 500 microg/mL NM, according to the study of Matthias Rath Research Institute(6).
The study at All India Institute of Medical Sciences, in the study of the effects of vitamin C in cervical cancer patients, indicated that vitamin C downregulates the redox sensitive transcription factor AP-1 and decreases one of its transcription targets HPV E6, and stabilizes P53 through increase in Bax and decrease in Bcl-2 and telomerase activity(7). In deed, the study at Kidwai Memorial Institute of Oncology also found s significant low levels of of carotene, vitamin A, and vitamin C measured in the serum of patients with cancer of the uterine cervix(8).
Other researchers suggested malnutrition may  be a significant cause for the increased prevalence of cervical cancer in women with evidences of low levels of GSH, GPx, GST, SOD, vitamin E and vitamin C in the circulation of cervical cancer patient(9).

Taking altogether, oral administration of vitamin C  may be associated to reduced risk and treatment of cervical cancer and precancer but malnutrition and nutrients deficiency may play an important role in enhancing the start of the cancer itself. Daily ingestion of high-dose vitamin C may be considered safe, but in rare incidence, overdoses in a prolonged period of time, may cause intra-renal oxalate crystal deposition, a fatal nephrotoxicity(10)(11).

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References
(1) Dietary factors and in situ and invasive cervical cancer risk in the European prospective investigation into cancer and nutrition study by González CA1, Travier N, Luján-Barroso L, Castellsagué X, Bosch FX, Roura E, Bueno-de-Mesquita HB, Palli D, Boeing H, Pala V, Sacerdote C, Tumino R, Panico S, Manjer J, Dillner J, Hallmans G, Kjellberg L, Sanchez MJ, Altzibar JM, Barricarte A, Navarro C, Rodriguez L, Allen N, Key TJ, Kaaks R, Rohrmann S, Overvad K, Olsen A, Tjønneland A, Munk C, Kjaer SK, Peeters PH, van Duijnhoven FJ, Clavel-Chapelon F, Boutron-Ruault MC, Trichopoulou A, Benetou V, Naska A, Lund E, Engeset D, Skeie G, Franceschi S, Slimani N, Rinaldi S, Riboli E.(PubMed)
(1a) Vitamin or antioxidant intake (or serum level) and risk of cervical neoplasm: a meta-analysis by Myung SK1, Ju W, Kim SC, Kim H; Korean Meta-analysis (KORMA) Study Group.(PubMed)
(1b) Intakes of vitamin A, C, and E, and beta-carotene are associated with risk of cervical cancer: a case-control study in Korea by Kim J1, Kim MK, Lee JK, Kim JH, Son SK, Song ES, Lee KB, Lee JP, Lee JM, Yun YM.(PubMed)
(1c) Vitamins C and E and beta carotene supplementation and cancer risk: a randomized controlled trial by Lin J1, Cook NR, Albert C, Zaharris E, Gaziano JM, Van Denburgh M, Buring JE, Manson JE.(PubMed)
(2) [Effect of antioxidant supplementation over oxidative stress and quality of life in cervical cancer].
[Article in Spanish] by Fuchs-Tarlovsky V1, Bejarano-Rosales M, Gutiérrez-Salmeán G, Casillas MA, López-Alvarenga JC, Ceballos-Reyes GM.(PubMed)
(3) Selective suppression of cervical cancer Hela cells by 2-O-β-D-glucopyranosyl-L-ascorbic acid isolated from the fruit of Lycium barbarum L by Zhang Z1, Liu X, Wu T, Liu J, Zhang X, Yang X, Goodheart MJ, Engelhardt JF, Wang Y.(PubMed
(4) Dietary intakes of selected nutrients and food groups and risk of cervical cancer by Ghosh C1, Baker JA, Moysich KB, Rivera R, Brasure JR, McCann SE.(PubMed
(4a) Involvement of oxidative stress in the pre-malignant and malignant states of cervical cancer in women by Gonçalves TL1, Erthal F, Corte CL, Müller LG, Piovezan CM, Nogueira CW, Rocha JB.(PubMed)
(5) Oxidative stress and antioxidant status in cervical cancer patients by Naidu MS1, Suryakar AN, Swami SC, Katkam RV, Kumbar KM.(PubMed
(6) Suppression of human cervical cancer cell lines Hela and DoTc2 4510 by a mixture of lysine, proline, ascorbic acid, and green tea extract by Roomi MW1, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M.(PubMed
(7) Vitamin C augments chemotherapeutic response of cervical carcinoma HeLa cells by stabilizing P53 by Reddy VG1, Khanna N, Singh N.(PubMed
(8) Serum carotene, vitamin A, and vitamin C levels in breast cancer and cancer of the uterine cervix by Ramaswamy G1, Krishnamoorthy L.(PubMed)
(9) Circulating lipid peroxidation and antioxidant status in cervical cancer patients: a case-control study by Manju V1, Kalaivani Sailaja J, Nalini N.(PubMed
(10) Fatal vitamin C-associated acute renal failure by McHugh GJ, Graber ML, Freebairn RC.(PubMed)
(11) Ascorbic acid overdosing: a risk factor for calcium oxalate nephrolithiasis by Urivetzky M, Kessaris D, Smith AD.(PubMed)




Monday, April 21, 2014

Cervical cancer in Vitamin A Points of View

 Kyle J. Norton(Draft Article)

Vitamins form an important part in human diet. Epidemiological studies, linking vitamin A in reduced risk of cervical cancer have produced uncleared result(1)(5)(8)(9). But in certain studies, vitamin A in form of retinoids and carotenoids is effective in inhibition of cervical  cancer cell lines through many anti porfilerative and apoptotic pathways.

Vitamin A is a general term of Vitamin A Retinol, retinal, beta-carotene, alpha-carotene, gamma-carotene, and beta-cryptoxanthin best known for its functions for vision health and antioxidant scavenger and essential for growth and differentiation of a number of cells and tissues.


1. The serum of vitamin A
In a total of 144 cervical cancer cases and 288 age-matched, hospital-based controls using unconditional logistic regression models showed a statistically lower mean dietary intakes of vitamin A compared to control(2). Other study found that serum and urine collected  are lower from12 women diagnosed with cervical intraepithelial neoplasia(3)(4)(4a). But the study of Nizam Institute of Medical Sciences, showed no correction of levels of vitamin A intake between cervical cancer patients and normal controls, in a total of total of 60 consecutive patients and 60 controls were enrolled from a referral hospital during the year 2004(6)(7).

2. Retinols
A combination of retinoids with histone deacetylase (HDAC) inhibitors effectively inhibited the growth of cervical cancer cells  due to the restore RARβ2 expression, associated with a significant upregulation of p21(CIP1) and p53 as well as a pronounced decrease in p-Stat3(10). In cervical cancer cells line HeLa and CaSki, All-trans retinoic acid (ATRA) derived from retinols, inhibited the proliferation of cervical cancer cells line HeLa but showed no effect on proliferation CaSki cells(11).
Other derivatives of retinols, all-trans and 9-cis retinoic acid induced profilerative activity of CaSki cells through cell cycle arrest via exhibited the increase in the level of immunophenotypic expression of wild type p53 and inhibited E6/E7 transcription(12). the study of composition of tea polyphenol, (-)-epigallocatechin gallate (EGCG) and retinoic acid (RA), showed to prevent cervical adenocarcinoma, though induced apoptosis and inhibited telomerase activity(13).

3. Carotenoids
According to the University of Arizona, in the analysis of cervical tissue (cancerous, precancerous, and noncancerous) samples obtained from 87 patients (age, 21-86 years), showed that maintaining an adequate serum concentration of beta-carotene may be necessary for the prevention of cervical cancer and precancer(14). Crocetin is a natural carotenoid dicarboxylic acid, inhibited the cell profileration of Hela cells through cell cycle arrest via p53-dependent and -independent mechanisms(15). According to Albert Einstein College of Medicine and Montefiore Medical Center, showed a lower correction of mean plasma levels of carotenoids (beta-carotene, lycopene, and canthaxanthin), as well as alpha-tocopherol, in women with cervical intraepithelial neoplasia (CIN)and cervical cancer and suggested that antioxidant deficiency may be associated to the pathogenesis of CIN and carcinoma of the cervix(16). Dr. Harris RW, and the researcher team in the study of Cancer of the cervix uteri and vitamin A indicated the strong correction of significantly reduced serum beta carotene concentrations in in women with pre-invasive disease compared to the controls(17).

Taking altogether, Vitamin A may be associated to reduced risk and treatment of cervical cancer, but further studies are necessary to validate its effectiveness. maintaining the adequate levels of vitamin A may be a choice to prevent the disease from start. Recommended intakes of vitamin A, according to  the Institute of Medicine of the National Academies (formerly National Academy of Sciences) is 600 µg daily as extremely high doses (>9000 mg) can be toxicity as causes of dry, scaly skin, fatigue, nausea, loss of appetite, bone and joint pains, headaches, etc.

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References
(1) Dietary factors and in situ and invasive cervical cancer risk in the European prospective investigation into cancer and nutrition study by González CA1, Travier N, Luján-Barroso L, Castellsagué X, Bosch FX, Roura E, Bueno-de-Mesquita HB, Palli D, Boeing H, Pala V, Sacerdote C, Tumino R, Panico S, Manjer J, Dillner J, Hallmans G, Kjellberg L, Sanchez MJ, Altzibar JM, Barricarte A, Navarro C, Rodriguez L, Allen N, Key TJ, Kaaks R, Rohrmann S, Overvad K, Olsen A, Tjønneland A, Munk C, Kjaer SK, Peeters PH, van Duijnhoven FJ, Clavel-Chapelon F, Boutron-Ruault MC, Trichopoulou A, Benetou V, Naska A, Lund E, Engeset D, Skeie G, Franceschi S, Slimani N, Rinaldi S, Riboli E.(PubMed)
(2) Intakes of vitamin A, C, and E, and beta-carotene are associated with risk of cervical cancer: a case-control study in Korea by Kim J1, Kim MK, Lee JK, Kim JH, Son SK, Song ES, Lee KB, Lee JP, Lee JM, Yun YM.(PubMed)
(3) Rapid HPLC method for the determination of vitamin A and E and cotinine concentration in human serum in women with CIN and cervical cancer by Bystrowska B1, Gomółka E, Szczudrawa A, Brandys J, Pawlik M, Milewicz T, Dulińska-Litewka J, Jach R.(PubMed)
(4) A case-control study of nutrient status and invasive cervical cancer. I. Dietary indicators.
Herrero R1, Potischman N, Brinton LA, Reeves WC, Brenes MM, Tenorio F, de Britton RC, Gaitan E.(PubMed)
(4a) Dietary risk factors for invasive and in-situ cervical carcinomas in Bangkok, Thailand by Shannon J1, Thomas DB, Ray RM, Kestin M, Koetsawang A, Koetsawang S, Chitnarong K, Kiviat N, Kuypers J.(PubMed)
(5) Intakes of vitamin A, C, and E, and beta-carotene are associated with risk of cervical cancer: a case-control study in Korea(5)Kim J1, Kim MK, Lee JK, Kim JH, Son SK, Song ES, Lee KB, Lee JP, Lee JM, Yun YM.(PubMed)
(6) Food consumption pattern in cervical carcinoma patients and controls by Labani L1, Andallu B, Meera M, Asthana S, Satyanarayana L.(PubMed)
(7) Dietary micronutrients and cervical dysplasia in southwestern American Indian women by Buckley DI1, McPherson RS, North CQ, Becker TM.(PubMed)
(8) Antioxidant vitamins and mineral supplementation, life span expansion and cancer incidence: a critical commentary by Dolara P1, Bigagli E, Collins A.(PubMed)
(9) Vitamin A and risk of cervical cancer: a meta-analysis by Zhang X1, Dai B, Zhang B, Wang Z.(PubMed)
(10) Combination of valproic acid and ATRA restores RARβ2 expression and induces differentiation in cervical cancer through the PI3K/Akt pathway by Feng D1, Cao Z, Li C, Zhang L, Zhou Y, Ma J, Liu R, Zhou H, Zhao W, Wei H, Ling B.(PubMed)
(11) Proliferation of cells and expression of RARs, RXRs and HPV viral E6 and E7 proteins in cervical cancer cell lines after treatment with ATRA by Myga-Nowak M1, Pacholska-Bogalska J, Kwaśniewski W, Kwaśniewska A, Goździcka-Józefiak A.(PubMed)
(12) The effect of all-trans and 9-cis retinoic acid on the steady state level of HPV16 E6/E7 mRNA and cell cycle in cervical carcinoma cells by Narayanan BA1, Holladay EB, Nixon DW, Mauro CT.(PubMed)
(13) Antiproliferative effects of the major tea polyphenol, (-)-epigallocatechin gallate and retinoic acid in cervical adenocarcinoma by Yokoyama M1, Noguchi M, Nakao Y, Ysunaga M, Yamasaki F, Iwasaka T.(PubMed)
(14) Concentrations of carotenoids, tocopherols, and retinol in paired plasma and cervical tissue of patients with cervical cancer, precancer, and noncancerous diseases by Peng YM1, Peng YS, Childers JM, Hatch KD, Roe DJ, Lin Y, Lin P.(PubMed)
(15) Crocetin induces cytotoxicity and enhances vincristine-induced cancer cell death via p53-dependent and -independent mechanisms by Zhong YJ1, Shi F, Zheng XL, Wang Q, Yang L, Sun H, He F, Zhang L, Lin Y, Qin Y, Liao LC, Wang X.(PubMed)
(16) Plasma levels of beta-carotene, lycopene, canthaxanthin, retinol, and alpha- and tau-tocopherol in cervical intraepithelial neoplasia and cancer by Palan PR1, Mikhail MS, Goldberg GL, Basu J, Runowicz CD, Romney SL.(PubMed)
(17) Cancer of the cervix uteri and vitamin A byb Harris RW, Forman D, Doll R, Vessey MP, Wald NJ.(PubMed)

Sunday, April 20, 2014

Cervical cancer in Foods Points of View

Kyle J. Norton(Draft Article)

Cervix is the lower part of uterus that opens at the top of the vagina. Cervix acts an transition area for vaginal lining (squamous epithelium) change to uterus type (columnar epithelium) through the transitional area (squamous columnar epithelium) to host the development of the fetus. Cervical cancer is malignant neoplasm of the cervix uteri or cervical area caused by abnormal cells growth with alternation of cells DNA. According to the American Cancer Society's, in 2014, 12,360 new cases of invasive cervical cancer will be diagnosed with the death of  4,020 patients. The risk of cervical cancer is higher in Hispanic women followed by African-Americans, Asians and Pacific Islanders, and whites(a).
Depending to the stage and grade of the cancer, if the cancer is found in the early stahe, hysterectomy may not be needed. Other while  after sugery, chemotherapy including Cisplatin, Fluorouracil (5-FU), Mitomycin, Paclitaxel, Ifosfamide, Carboplatin, Bevacizumab and radiotherapy may be necesary, but with certain side effects.  emerging suggestion of a healthy and balanced diet to improve high serum levels of antioxidants may reduce cervical neoplasia risk(b)(c)  but other suggested that the role of diet and nutrition in the etiology of cervical cancer is not yet resolved(d) and Catalan Institute of Oncology study showed statistically nonsignificant inverse associations were also observed for leafy vegetables, root vegetables, garlic and onions, citrus fruits, vitamin C, vitamin E and retinol for invasive squamous cervical cancer (ISC)(e).

Epidemiological studies, linking foods in reduced risk of cerical cancer have been inconsistent. but certain foods have found effectively in reduced risk and treatment of cervical cancer.

1. Cruciferous vegetablesCruciferous vegetables are the group of vegetables belonging to the family Brassicaceae, including cauliflower, cabbage, cress, bok choy, broccoli etc.
Isothiocyanates, a majpr chemical constituent found in Cruciferous vegetables, inhibited the cell viability of human cervical cancer cells, through improvement of antioxidant status(1). β-Phenylethyl isothiocyanate (PEITC). induced apoptosis to inhibit cell proliferation in human cervical cancer cell lines (HEp-2 and KB), through increased the expression of the death receptors (DR4 and DR5) and cleaved caspase-3(2).  Other chemical compouds,  I3C (indole-3-carbinol) and DIM (diindolylmethane) found in all types of cruciferous vegetables, demonstrated exceptional anti-cancer effects against hormone responsive cancers such as ovarian cancers(3). Some reseachers suggested that isothiocyanates and indoles through intake of cruciferous vegetable consumption may decrease cancer risk, but the protective effects may be influenced by individual genetic variation (polymorphisms) in the metabolism and elimination of isothiocyanates from the body and in some in instances, long term rxposure to sulforaphane and indole-3-carbinol (I3C), may be implicated in a variety of anticarcinogenic mechanisms(4).

2. Tomato
Tomato is a red, edible fruit, genus Solanum, belonging to family Solanaceae, native to South America. Because of its health benefits, tomato is grown world wide for commercial purpose and often in green house.
Glycoalkaloid-rich green tomato extracts, according to the Seowon University inhibited ptofileration of HeLa cervical carcinoma cells through inactivation(5). Dr Ferguson LR, in the study of Prospects for cancer prevention, suggested that Fruit and vegetable servings should total a minimum of five each day. Some specific fruits and vegetables (e.g., tomato, broccoli, onions) may have particular benefits against individual cancer types(6). But the reviews of FDA in 2004, of some studies of indication of an inverse association between tomato and/or lycopene intake and the risk of some types of cancer, suggested that there are no credible evidence for an association between tomato consumption and a reduced risk of lung, colorectal, breast, cervical, or endometrial cancer(7).

3. Garlic
Garlic is a natural superfood healer for its natural antibiotic with antiviral, antifungal, anticoagulant and antiseptic properties.
Diallyl sulfide (DAS), a chemical component of garlic induced mitochondrial dysfunction, leading to the release of cytochrome c for causing apoptosis in human cervical cancer Ca Ski cells(8) and cell cycle arrest and apoptosis through the p53, caspase- and mitochondria-dependent pathways in in HeLa human cervical cancer cells(9). The Defense Food Research Laboratory study indicated that Garlic exerted its anticarcinogenic effect(including cervical cancer) through a number of mechanisms, including scavenging of radicals, increasing gluathione levels, increasing the activities of enzymes(10). In 3-methylcholanthrene (MCA)-induced carcinogenesis in the uterine cervix of virgin young adult Swiss albino mice study, found a sginificant decline in the incidence of carcinoma witjh oral administration of garlic at the dose level of 400 mg/kg body wt./day for 2 weeks before and 4 weeks following carcinogen thread insertion(11).

4. Ginger
Ginger (Zingiber officinale) or ginger root is the genus Zingiber, belonging to the family Zingiberaceae, native to Tamil. It has been used in traditional and Chinese medicine to treat dyspepsia, gastroparesis, constipation, edema, difficult urination, colic, etc.
Crude methanol and fractionated extract of the rhizomes of Alpinia pahangensis, a wild ginger distributed in the lowlands of Pahang, Malaysia, showed potent cytotoxic effect against certain cancer cell lines, including human cervical cancer cell line, Ca Ski(12). In human cervical epithelial carcinoma (HeLa), aqueous extract of ginger (GAE) induced apoptosis of cancer cells through interacted directly with cellular microtubules and disrupts its structure(13). Other study indicated that
Benjakul [BEN], a composeition of five plants: Piper chaba fruit [PC], Piper sarmentosum root [PS], Piper interruptum stem [PI], Plumbago indica root [PL] and Zingiber officinale rhizome [ZO] in Thai herbal medicine, showed to extert its cytotoxic activity against certain types of cnacer cell line including cervial cancer cell line Hela(14).

5. Carrot
Carrot can grow to 3ft tall. It is root vegetable with orange color normally, a sub spices of Daucus carota, belongs to the family Apiaceae, native to Asian and Europe.
According to Aichi Cancer Center, frequent intakes of carrot are associated decreased risk of cervical cancer(15). The Shandong University study in assessing the risk of cervical cancer association of vitamin A found a abundantly in carrot (retinol, carotene and other carotenoids) intake or blood (serum or plasma) levels of vitamin A (retinol and carotene), indicated that vitamin A intake and blood vitamin A levels are inversely associated with the risk of cervical cancer(16). Others in the testing of concentrations of retinol and beta carotene in serum samples taken from 113 women with cervical cancer, 32 with invasive and 81 with pre-invasive disease, and compared with those from 226 age-matched control women found a significantly reduced concentration of beta carotene levels in women with pre-invasive disease compared to the control(17).

6. Dulse
Dulse is a red seaweed of genus Palmaria, belong to Family Palmariaceae that grows attached to rocks by a "holdfast" in the North Atlantic and Northwest Pacific. It is commonly used in Ireland and Atlantic Canada both as food and medicinally and is now shipped around the globe. Dulse is found in many health food stores or fish markets or can be ordered directly from local distributors.
Ryerson University study of the extracts from variety of edible seaweeds, showed a positive effect of dulse polyphenols in inhibited on cell proliferation on human cervical adenocarcinoma cell line (HeLa cells) through its antioxidant activity(18)(19). Fucoxanthin found abundantly in dulse, in the study by Henan University, showed to exert autophagy-dependent cytotoxic effect in cervical cancer cell lines HeLa cells via inhibition of Akt/mTOR signaling pathway(20).

8. Strawberry
Strawberries is a genius of Fragaria × ananassa belongs to the family Roseaceae. They have been grown all over the world with suitable climate for commercial profits and for health benefits.
The study of the effects of variety of berry extracts in human cervical cancer (HeLa) cells, indicated that
tannin-rich fraction of procyanidins of strawberry extract are most potent in comparison with other berries(21). Other study of the effects of the extract of Strawberry, Blueberry, and Raspberry Extracts. showed a positive effects of ethanol extracts from all four fruits strongly inhibited CaSki and SiHa cervical cancer cell lines(22).

9. Grape and Red wine
Grape is a woody vines of the genus Vitis, belong to the family Vitaceae, native to southern Turkey. Grape extracts was found to interact effectively with decaffeinated green tea extracts both in the inhibition of tNOX activity and in the inhibition of cancer cell growth(23). Red and white wine polyphenols and resveratrol exerted higher cytotoxic activity against HeLabut white wine polyphenolic extract exhibited a significantly higher antiproliferative action on cancer cell lines than red wine extract(24).

10. Cactus pear
Cactus pear also known as Prickly pear is a genus Opuntia, belonging to the family Cactaceae, native to Mexico.
Cactus pear extracts, in the study of immortalized ovarian and ovarian cancer cells (OVCA420, SKOV3), exhibited anti ptoliferative effect through a dramatic increase of reactive oxygen species (ROS), induced DNA fragmentation, together with a perturbed expression of apoptotic-related (Bax, Bad, caspase 3, Bcl2, p53, and p21) and ROS-sensitive (NF-kappaB, c-jun/c-fos) genes(25). Other study from the University of Arizona, indicated that aqueous extracts of cactus pear significant increase in apoptosis and growth inhibition in both immortalized epithelial cells and cancer cells in a dose- and time-dependent manner through cell cycle arrest(26).

11.  Vitis coignetiae Pulliat
Vitis coignetiae Pulliat also known as Yamabudo, Crimson Glory Vine, is the genus Viti, belonging to the family Vitaceae, native to the temperate climes of Asia. It has been used as a health juice and wine because of the abundant polyphenols and anthocyanins.
Anthocyanins from fruits of Vitis coignetiae Pulliat (AIMs), inhibited the invasion of HeLa cell in a dose-dependent manner, through suppressing NF- κ B-regulated genes and EMT, which relates to suppression of I κ B α phosphorylation and GSK-3 activity(26). In stem extracts from Greek Vitis vinifera varieties of the total polyphenolic content (TPC) found to  stem extracts inhibited at low concentrations the growth of HepG2 and HeLa cancer cells comparable to those of seed extracts(27)(28).

12. Fatty fish
Fatty fish containing a large amounts of omega-3, 6 fatty acids may be associated to reduced risk of cancers. Docosahexaenoic acids (DHA) found in fish oil plays important roles in reduced the progression of carcinogenesis, including human cervical cancer cell line, HeLa(29), through cytotoxic effects(30). Unluckily, n the study of the relationship between dietary fat and cancer, researchers at the Fred Hutchinson Cancer Research Center, indicated that fish omega-3 polyunsaturated fat had a nonsignificant negative association with the cancer(31)

13. Green Tea
Green tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world.
In a total of  104 patients diagnosed with cervical cancer or cervical intraepithelial neoplasias (CINII/III)936 healthy women selected from the Wufeng area, showed a positive effect of green tea in reduced risk of Green tea intake in cervical cancer or CINII/III(32).  (-)-epigallocatechin-3-gallate (EGCG), a major chemical compound in green tea, inhibited the proliferation of human cervical cancer cell line, CaSki through induction of apoptosis and cell cycle arrest as well as regulation of gene expression(33). In other huamun cervical cancer cell line,  HeLa, (-)-epigallocatechin-3-gallate (EGCG), showed it anti proliferative effects through reduced mRNA expression of FTS via p53(34).

14. Organic soybean
Soybean is genus Glycine, the family Fabaceae, one of the legumes that contains twice as much protein per acre as any other major vegetable or grain crop, native to Southeast Asia. Now, it is grown worldwide with suitable climate for commercial profit and a healthy foods.
In female athymic mice, germinated soy protein inhibited the proliferation of cervical cancer cell line HeLa,  through generation of biologically active peptides(35). via down-regulated PTTG1 and TOP2A mRNA expression (two genes considered as therapeutic targets) and induced apoptosis in cancer cells(36). Isoflavones , the major bioactive compounds found in organic soy,  the derived isoflavone mixture(SI-I) containing 71% daidzein, 14.3% genistein and 14.7% glycitein inhibited  HeLa cell growth through inducing apoptosis via the mitochondrial pathway(37).

Taking altogether, without going into reviews, the list of foods above may be potent in reduced risk and treatment of cervical cancer. But further studies with large sample sizes and multi centers are necessary to improve the validation of these claims. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying
 
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References
(a) Cerical cancer (Amerrican cancer society)
(b) Diet and serum micronutrients in relation to cervical neoplasia and cancer among low-income Brazilian women by Tomita LY1, Longatto Filho A, Costa MC, Andreoli MA, Villa LL, Franco EL, Cardoso MA; Brazilian Investigation into Nutrition and Cervical Cancer Prevention (BRINCA) Study Team.(PubMed)
(c) Associations of dietary dark-green and deep-yellow vegetables and fruits with cervical intraepithelial neoplasia: modification by smoking by Tomita LY1, Roteli-Martins CM, Villa LL, Franco EL, Cardoso MA; BRINCA Study Team.(PubMed)
(d) Diet and the risk of in situ cervical cancer among white women in the United States by Ziegler RG1, Jones CJ, Brinton LA, Norman SA, Mallin K, Levine RS, Lehman HF, Hamman RF, Trumble AC, Rosenthal JF, et al.(PubMed)
(e) Dietary factors and in situ and invasive cervical cancer risk in the European prospective investigation into cancer and nutrition study by González CA1, Travier N, Luján-Barroso L, Castellsagué X, Bosch FX, Roura E, Bueno-de-Mesquita HB, Palli D, Boeing H, Pala V, Sacerdote C, Tumino R, Panico S, Manjer J, Dillner J, Hallmans G, Kjellberg L, Sanchez MJ, Altzibar JM, Barricarte A, Navarro C, Rodriguez L, Allen N, Key TJ, Kaaks R, Rohrmann S, Overvad K, Olsen A, Tjønneland A, Munk C, Kjaer SK, Peeters PH, van Duijnhoven FJ, Clavel-Chapelon F, Boutron-Ruault MC, Trichopoulou A, Benetou V, Naska A, Lund E, Engeset D, Skeie G, Franceschi S, Slimani N, Rinaldi S, Riboli E.(PubMed)
(1) The anti-oxidant properties of isothiocyanates: a review by de Figueiredo SM1, Filho SA, Nogueira-Machado JA, Caligiorne RB.(PubMed)
(2) Effect of β-phenylethyl isothiocyanate from cruciferous vegetables on growth inhibition and apoptosis of cervical cancer cells through the induction of death receptors 4 and 5 by Huong le D1, Shim JH, Choi KH, Shin JA, Choi ES, Kim HS, Lee SJ, Kim SJ, Cho NP, Cho SD(PubMed)
(3) Chemopreventive properties of indole-3-carbinol, diindolylmethane and other constituents of cardamom against carcinogenesis by Acharya A1, Das I, Singh S, Saha T.(PubMed)
(4) Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis by Higdon JV1, Delage B, Williams DE, Dashwood RH.(PubMed)
(5) Changes in free amino acid, phenolic, chlorophyll, carotenoid, and glycoalkaloid contents in tomatoes during 11 stages of growth and inhibition of cervical and lung human cancer cells by green tomato extracts by Choi SH1, Lee SH, Kim HJ, Lee IS, Kozukue N, Levin CE, Friedman M.(PubMed)
(6) Prospects for cancer prevention by Ferguson LR.(PubMed)
(7) The U.S. Food and Drug Administration's evidence-based review for qualified health claims: tomatoes, lycopene, and cancer by Kavanaugh CJ1, Trumbo PR, Ellwood KC.(PubMed)
(8) Diallyl sulfide promotes cell-cycle arrest through the p53 expression and triggers induction of apoptosis via caspase- and mitochondria-dependent signaling pathways in human cervical cancer Ca Ski cells by Chiu TH1, Lan KY, Yang MD, Lin JJ, Hsia TC, Wu CT, Yang JS, Chueh FS, Chung JG.(PubMed)
(9) Diallyl sulfide induces cell cycle arrest and apoptosis in HeLa human cervical cancer cells through the p53, caspase- and mitochondria-dependent pathways by Wu PP1, Chung HW, Liu KC, Wu RS, Yang JS, Tang NY, Lo C, Hsia TC, Yu CC, Chueh FS, Lin SS, Chung JG.(PubMed)
(10) Anticarcinogenic properties of garlic: a review by Khanum F1, Anilakumar KR, Viswanathan KR.(PubMed)
(11) Chemopreventive action of garlic on methylcholanthrene-induced carcinogenesis in the uterine cervix of mice by Hussain SP1, Jannu LN, Rao AR.(PubMed)
(12) Antioxidant potential, cytotoxic activity and total phenolic content of Alpinia pahangensis rhizomes by Phang CW1, Malek SN, Ibrahim H.(PubMed)
(13) Aqueous extract of ginger shows antiproliferative activity through disruption of microtubule network of cancer cells by Choudhury D1, Das A, Bhattacharya A, Chakrabarti G.(PubMed)
(14) In vitro cytotoxic activity of Benjakul herbal preparation and its active compounds against human lung, cervical and liver cancer cells by Ruangnoo S1, Itharat A, Sakpakdeejaroen I, Rattarom R, Tappayutpijam P, Pawa KK.(PubMed)
(15) [Hospital epidemiology--a comparative case control study of breast and cervical cancers].
[Article in Japanese] by Tajima K1, Hirose K, Ogawa H, Yoshida M, Ohta M.(PubMed)
(16) Vitamin A and risk of cervical cancer: a meta-analysis by Zhang X1, Dai B, Zhang B, Wang Z.(PubMed
(17) Cancer of the cervix uteri and vitamin A by Harris RW, Forman D, Doll R, Vessey MP, Wald NJ.(PubMed
(18) Antioxidant and antiproliferative activities of extracts from a variety of edible seaweeds by Yuan YV1, Walsh NA.(PubMed
(19) Extracts from dulse (Palmaria palmata) are effective antioxidants and inhibitors of cell proliferation in vitro. by Yuan YV1, Carrington MF, Walsh NA.(PubMed
(20) Essential role of autophagy in fucoxanthin-induced cytotoxicity to human epithelial cervical cancer HeLa cells by Hou LL1, Gao C, Chen L, Hu GQ, Xie SQ.(PubMed
(21) Berry extracts exert different antiproliferative effects against cervical and colon cancer cells grown in vitro by McDougall GJ1, Ross HA, Ikeji M, Stewart D.(PubMed
(22) Anticarcinogenic Activity of Strawberry, Blueberry, and Raspberry Extracts to Breast and Cervical Cancer Cells. by Wedge DE1, Meepagala KM, Magee JB, Smith SH, Huang G, Larcom LL.(PubMed
(23) Anticancer activity of grape and grape skin extracts alone and combined with green tea infusions by Morré DM1, Morré DJ.(PubMed
(24) Cytotoxic effect of wine polyphenolic extracts and resveratrol against human carcinoma cells and normal peripheral blood mononuclear cells by Matić I1, Zizak Z, Simonović M, Simonović B, Godevac D, Savikin K, Juranić Z.(PubMed)
(25) Cactus pear extracts induce reactive oxygen species production and apoptosis in ovarian cancer cells by Feugang JM1, Ye F, Zhang DY, Yu Y, Zhong M, Zhang S, Zou C.(PubMed
(26) Cactus pear: a natural product in cancer chemoprevention by Zou DM1, Brewer M, Garcia F, Feugang JM, Wang J, Zang R, Liu H, Zou C.(PubMed)
(27) Anthocyanins from Vitis coignetiae Pulliat Inhibit Cancer Invasion and Epithelial-Mesenchymal Transition, but These Effects Can Be Attenuated by Tumor Necrosis Factor in Human Uterine Cervical Cancer HeLa Cells by Lu JN1, Lee WS, Yun JW, Kim MJ, Kim HJ, Kim DC, Jeong JH, Choi YH, Kim GS, Ryu CH, Shin SC.(PubMed)
(28) Assessment of polyphenolic content, antioxidant activity, protection against ROS-induced DNA damage and anticancer activity of Vitis vinifera stem extracts by Apostolou A1, Stagos D, Galitsiou E, Spyrou A, Haroutounian S, Portesis N, Trizoglou I, Wallace Hayes A, Tsatsakis AM, Kouretas D.(PubMed)
(29) Omega-3 but not omega-6 unsaturated fatty acids inhibit the cancer-specific ENOX2 of the HeLa cell surface with no effect on the constitutive ENOX1 by Morre J1, Morré DM, Brightmore R.(PubMed)
(30) Differential sensitivity of cancer cells to docosahexaenoic acid-induced cytotoxicity: the potential importance of down-regulation of superoxide dismutase 1 expression by Ding WQ1, Vaught JL, Yamauchi H, Lind SE.(PubMed)
(31) Types of dietary fat and the incidence of cancer at five sites by Hursting SD1, Thornquist M, Henderson MM.(PubMed)
(32) Case-control study of diet in patients with cervical cancer or precancerosis in Wufeng, a high incidence region in China by  Jia Y1, Hu T, Hang CY, Yang R, Li X, Chen ZL, Mei YD, Zhang QH, Huang KC, Xiang QY, Pan XY, Yan YT, Wang XL, Wang SS, Hang Z, Tang FX, Liu D, Zhou J, Xi L, Wang H, Lu YP, Ma D, Wang SX, Li S.(PubMed)
(33) A major constituent of green tea, EGCG, inhibits the growth of a human cervical cancer cell line, CaSki cells, through apoptosis, G(1) arrest, and regulation of gene expression by Ahn WS1, Huh SW, Bae SM, Lee IP, Lee JM, Namkoong SE, Kim CK, Sin JI.(PubMed)
(34) EGCG suppresses Fused Toes Homolog protein through p53 in cervical cancer cells by Muthusami S1, Prabakaran DS, An Z, Yu JR, Park WY.(PubMed)
(35) Effect of germinated soy protein on the growth of HeLa cervical cancer cells in female athymic mice by Robles-Ramírez Mdel C1, Ramón-Gallegos E, Reyes-Duarte FJ, Mora-Escobedo R.(PubMed)
(36) A peptide fraction from germinated soybean protein down-regulates PTTG1 and TOP2A mRNA expression, inducing apoptosis in cervical cancer cells by Robles-Ramírez Mdel C1, Ramón-Gallegos E, Mora-Escobedo R, Torres-Torres N.(PubMed)
(37) Soy-derived isoflavones inhibit HeLa cell growth by inducing apoptosis by Xiao JX1, Huang GQ, Geng X, Qiu HW.(PubMed)