Tuesday, March 18, 2014

Ovarian Cancer in Vitamin C Points of View

Ovarian cancer is defined as a condition of  abnormal ovarian cells growth of ovaries.  It is one of most common cancer in US,
According to the information of national cancer institute, in 2013 Us alone 22,240 women were diagnosed with the incidence of the disease with death of 14030.
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.

The conflict results
Epidemiological studies, linking vitamin C in reduced risk of endometrial cancer have produced inconsistent results. The Robert Wood Johnson Medical School study, indicated a little evidence of an association with dietary TAC or the others individual antioxidants, including vitamin C in reduced risk of epithelial ovarian cancer(1) But the University of Kansas Medical Center, showed a positive effects of vitamin C in inhibition and death in ovarian cancer cells. through multiple pathways. Composition of vitamin C and the conventional chemotherapeutic agents carboplatin, synergistically inhibited ovarian cancer in mouse models and reduced chemotherapy-associated toxicity in patients with ovarian cancer(2) and  AA at ≥250 μmol/L showed to completely inhibit serum-stimulated cell proliferation in all cell lines tested, including IOSE-385, OVCAR-3, and OVCA-432 which were was partially (∼10%-20%) countered by E2β and its metabolites(3). Other researchers suggested that ascorbic acid at the normal plasma concentration has an essential role in maintaining the NK cytotoxicity against ovarian cancer cells in mouse model and depletion of ascorbic acid may impair NK cell activity(4).

The effects
Arsenic trioxide (As2O3), a novel compound generated from the oxidation of arsenic routinely, and pharmacological doses of Ascorbic acid(AA), showed to inhibited ovarian cancer cells through manipulation of cellular glutathione (GSH) levels via enhancement of AA's cytotoxicit. These result indicated that depletion of GSH may promote the progression of the disease(5).In  in mice bearing glioblastoma xenograft, oral ascorbate administration, exhibited the production of sustained ascorbate radical and hydrogen peroxide formation selectively within interstitial fluids of tumors but not in blood and significantly decreased growth rates of ovarian cancer(6). In human ovarian cancer cell line SK-OV-3, the composition of lysine, proline, arginine, ascorbic acid and green tea extract inhibited the cancer development and invasion, possibly through MMP expression(7). According to American University of the Caribbean, combined treatments of  VC (ascorbic acid), VK3 (menadione) on the cellular and nuclear morphology and DNA content of a human ovarian carcinoma cell line (MDAH 2774), showed to inhibit the cancer cell line through generalized DNA degradation(8)(9).

Taking altogether, Vitamin C and its composition may b4 effective in reduced risk and treatment of ovarian cancer through activation of its antioxidant cytotoxicity in enhancement the effectiveness of either novel agents or chemical compounds. 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
(1) Total and individual antioxidant intake and risk of epithelial ovarian cancer by Gifkins D1, Olson SH, Paddock L, King M, Demissie K, Lu SE, Kong AN, Rodriguez-Rodriguez L, Bandera EV.(PubMed)
(2) High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy by Ma Y1, Chapman J, Levine M, Polireddy K, Drisko J, Chen Q.(PubMed)
(3) Estradiol 17β and its metabolites stimulate cell proliferation and antagonize ascorbic acid-suppressed cell proliferation in human ovarian cancer cells by Li HH1, Zhao YJ, Li Y, Dai CF, Jobe SO, Yang XS, Li XF, Patankar MS, Magness RR, Zheng J.(PubMed)
(4) Depletion of ascorbic acid impairs NK cell activity against ovarian cancer in a mouse model.
Kim JE1, Cho HS, Yang HS, Jung DJ, Hong SW, Hung CF, Lee WJ, Kim D.(PubMed)
(5) Differential augmentative effects of buthionine sulfoximine and ascorbic acid in As2O3-induced ovarian cancer cell death: oxidative stress-independent and -dependent cytotoxic potentiation by Ong PS1, Chan SY, Ho PC.(PubMed)
(6) Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice by Chen Q1, Espey MG, Sun AY, Pooput C, Kirk KL, Krishna MC, Khosh DB, Drisko J, Levine M.(PubMed)
(7) Inhibition of matrix metalloproteinase-2 secretion and invasion by human ovarian cancer cell line SK-OV-3 with lysine, proline, arginine, ascorbic acid and green tea extract by Roomi MW1, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M.(PubMed)
(8) Autoschizis: a new form of cell death for human ovarian carcinoma cells following ascorbate:menadione treatment. Nuclear and DNA degradation by Gilloteaux J1, Jamison JM, Lorimer HE, Jarjoura D, Taper HS, Calderon PB, Neal DR, Summers JL.(PubMed)



(9) The in vitro antitumor activity of vitamins C and K3 against ovarian carcinoma by von Gruenigen VE1, Jamison JM, Gilloteaux J, Lorimer HE, Summers M, Pollard RR, Gwin CA, Summers JL.(PubMed)

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