Effects of Vitamins E and C on Human BreastCancer Cell Growth in the Presence of Various Fatty Acids

To investigate the effects of antioxidative vitamins in combination with various fatty acids on breast cancer cell proliferation, MDA-MB231 human breast cancer cells were cultured for 3 days in the serum-free Iscove's modified Dulbecco's medium (IMDM) supplemented with 1.25mg/ml delipidized bovine serum albumin and 10㎍/ml insulin. Alpha-tocopherol, ascorbic acid or both vitamins were added to the medium at the concentrations of 10 and 50μM in the presence of 3μg/ml of oletic(Oa), linoleic(LA) α-linoleinic(LNA) and docosahexaenoic acid(DHA). Cell growth was reduced significantly by α-tocopherol in a dose-dependent manner, but not affected by ascorbic aicd. The four different fatty acids did not have significant effects on cell growth, although DHA exerted inhibitory effect on the growth after 1 day. However, the each fatty acid was well incorporated into celluar lipid as such or elongated forms. Addition of α-tocopherol remarkably increased its celluar contents and reduced cellular levels of thiobarbituric acid substances (TBARS) that were elevated notably in the presence of DHA in the culture media. But ascorbic acid addition did not change much of either cellular α-tocopherol or TBARS contents. northern blot hybridization showed that tumor supressor gene ρ53 was most highly expressed by the combination of ρ-tocopherol and DHA in 8 hours of cell culture. In conclusion , the growth inhibitory effect of vitamin E suggests that breast cancer cell proliferation is reduced by the mechanism other than cytotoxicity of lipid peroxide and it is related to expressionof tumor supprosser gene p53, that can be increased by both vitamin E and n-3 fatty acid, DHA.