Adjuvant vitamin E and ovarian cancer Public Deposited

http://ir.library.oregonstate.edu/concern/undergraduate_thesis_or_projects/6969z229w

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  • Cisplatin (CDDP) is a highly active platinum-containing chemotherapeutic agent for use against solid tumors, including ovarian. However, like most antitumor agents, CDDP use is accompanied by non-tumor tissue toxicities leading to unwanted side effects, including neuropathy. To date, the mechanism(s) for these side effects are undefined. However, the clinical features of CDDP neurotoxicity resemble those seen in vitamin E (alpha-tocopherol, aT) deficiency neuropathy. Using a preclinical model of epithelial ovarian cancer we tested the hypothesis that (1) CDDP depletes aT by an oxidative stress mechanism whereby platinum acts as a catalyst for lipid peroxidation thereby leading to aT-deficiency neuropathy, (2) adjuvant aT will prevent CDDP-mediated lipid peroxidation and aT depletion, and (3) adjuvant aT will improve CDDP antitumor efficacy. Tumor-bearing F344 rats were assigned to one of four treatment regimens: (1) saline, (2) aT, (3) CDDP, or (4) CDDP + aT. Our data indicates CDDP increases lipid peroxidation and decreases plasma and tissue aT levels and that adjuvant aT prevents CDDP-induced lipid peroxidation and aT depletion. In addition, adjuvant aT decreased tumor tissue proliferation and decreased tumor burden more than 5-fold, compared to CDDP alone. These data are the first to document the ability of adjuvant aT to improve chemotherapeutic antitumor efficacy and improve antioxidant/oxidative stress status in an immune competent tumor-bearing animal.
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