Saturday, 22 March 2014

Ovarian Cancer in Vitamin E Points of View

By Kyle J. Norton

Ovarian cancer is defined as a condition of  abnormal ovarian cells growth of ovarian cells,  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 were diagnosed with ovarian cancer and 13,850 deaths.

Depending to the stage and grade of the cancer, chemotherapy such as cisplatin, carboplatin, paclitaxel, liposomal doxorubicin may be necessary to prevent the spread and recurrence of the cancer. Epidemiological studies focusing in vegetables and fruits in reduced risk and treatment of ovarian cancer have not been conclusive(a)(b)(c)(d), some herbs have showed to inhibit the progression of cancer with little or no side effects.

 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(2), 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.

Epidemiological studies, linking serum of vitamin E in the risk of ovarian cancer have produced inconsistent results.  Serum levels of vitamin are not associated to ovarian cancer risk, according to Tampere University Central Hospital and (1) but the study by Johns Hopkins University School of Hygiene and Public Health, indicated that the higher serum alpha-tocopherol levels are associated with an increased risk of ovarian cancer but diminished after adjustment for cholesterol(2). Other study suggested that lower alpha-tocopherol concentrations may be associated with the toxicity of  chemotherapy(3).

Alpha-TEA , a novel vitamin E analogue found to induce apoptosis a wide variety of epithelial cancer cell types, including breast, prostate, lung, colon, ovarian, cervical, and endometrial in cell culture and inhibit tumor burden and metastasis in a syngeneic mouse mammary tumor model,(4). Other study suggested that vitamin E derivative, vitamin E succinate (VES; RRR-alpha-tocopheryl succinate), and a vitamin E analogue alpha-TEA can induce A2780 and subline A2780/cp70 ovarian cancer cells to undergo DNA synthesis arrest within 24 h of treatment, excluding normal human mammary epithelial cells(5). In SK-OV-3 human ovarian adenocarcinoma along with its multi-drug resistant version SK-OV-3-paclitaxel-resistant (TR) cells, combination treatment of vitamin E co-loaded with curcumin and paclitaxel(a mitotic inhibitor) exhibited  a three-fold tumor inhibition with each of these cell lines(6). According to the University of Strathclyde, intravenous administration tocotrienol-rich fraction (TRF), showed to exhibit tumor regression and improved animal survival in a murine xenograft model(7). In MDAH2774 human ovarian cancer cells combined treatment of Adenovirus-mediated mda-7 (Ad-mda7) plus VES inhibited tumor progression through activation of two apoptotic extrinsic and intrinsic pathways (specifically Fas expression and cleavage of Bid and caspase-8 and disruption of mitochondrial in activation of downstream capase-9 and caspase-3 via cytochrome C releasE) but not the normal fibroblasts(8). and treatment with Ad-mda7-mediated alone induced apoptosis of  human ovarian cancer cells via activation of the Fas-FasL signaling pathway(9).

Taking altogether,  vitamin E succinate and analogue may be effective in reduced risk and treatment of ovarian cancer. Large sample size and multi center studies to validate the claims are necessary. 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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(a) Fruit and vegetable consumption and risk of epithelial ovarian cancer: the European Prospective Investigation into Cancer and Nutrition by Schulz M1, Lahmann PH, Boeing H, Hoffmann K, Allen N, Key TJ, Bingham S, Wirfält E, Berglund G, Lundin E, Hallmans G, Lukanova A, Martínez Garcia C, González CA, Tormo MJ, Quirós JR, Ardanaz E, Larrañaga N, Lund E, Gram IT, Skeie G, Peeters PH, van Gils CH, Bueno-de-Mesquita HB, Büchner FL, Pasanisi P, Galasso R, Palli D, Tumino R, Vineis P, Trichopoulou A, Kalapothaki V, Trichopoulos D, Chang-Claude J, Linseisen J, Boutron-Ruault MC, Touillaud M, Clavel-Chapelon F, Olsen A, Tjønneland A, Overvad K, Tetsche M, Jenab M, Norat T, Kaaks R, Riboli E.(PubMed)
(b) Fruits and vegetables and ovarian cancer risk in a pooled analysis of 12 cohort studies by Koushik A1, Hunter DJ, Spiegelman D, Anderson KE, Arslan AA, Beeson WL, van den Brandt PA, Buring JE, Cerhan JR, Colditz GA, Fraser GE, Freudenheim JL, Genkinger JM, Goldbohm RA, Hankinson SE, Koenig KL, Larsson SC, Leitzmann M, McCullough ML, Miller AB, Patel A, Rohan TE, Schatzkin A, Smit E, Willett WC, Wolk A, Zhang SM, Smith-Warner SA(PubMed).
(c) Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk by Riboli E1, Norat T.(PubMed)
(d) Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids: a prospective analysis by Fairfield KM1, Hankinson SE, Rosner BA, Hunter DJ, Colditz GA, Willett WC.(PubMed)
(1) Serum vitamins A and E and carotene in patients with gynecologic cancer by Heinonen PK1, Kuoppala T, Koskinen T, Punnonen R.(PubMed)
(2) Prospective study of serum micronutrients and ovarian cancer by Helzlsouer KJ1, Alberg AJ, Norkus EP, Morris JS, Hoffman SC, Comstock GW.(PubMed)
(3) Serum alpha-tocopherol, retinol and neopterin during paclitaxel/carboplatin chemotherapy by Melichar B1, Kalábová H, Krcmová L, Urbánek L, Hyspler R, Malírova E, Solichová D.(PubMed)
(4) Vitamin E and breast cancer by Kline K1, Yu W, Sanders BG.(PubMed)
(5) Differential response of human ovarian cancer cells to induction of apoptosis by vitamin E Succinate and vitamin E analogue, alpha-TEA by Anderson K1, Simmons-Menchaca M, Lawson KA, Atkinson J, Sanders BG, Kline K.(PubMed)
(6) Polyethylene glycol-phosphatidylethanolamine (PEG-PE)/vitamin E micelles for co-delivery of paclitaxel and curcumin to overcome multi-drug resistance in ovarian cancer by Abouzeid AH1, Patel NR1, Torchilin VP2(PubMed)
(7) Tumor regression after systemic administration of tocotrienol entrapped in tumor-targeted vesicles by Fu JY1, Blatchford DR, Tetley L, Dufès C.(PubMed)
(8) Vitamin E succinate in combination with mda-7 results in enhanced human ovarian tumor cell killing through modulation of extrinsic and intrinsic apoptotic pathways by Shanker M1, Gopalan B, Patel S, Bocangel D, Chada S, Ramesh R.(PubMed)
(9) Activation of the Fas-FasL signaling pathway by MDA-7/IL-24 kills human ovarian cancer cells by Gopalan B1, Litvak A, Sharma S, Mhashilkar AM, Chada S, Ramesh R.(PubMed)

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