EGCG and Omega-3 Fatty Acids Impact on Fatty Acid Synthase Activity in the Prosta

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DESCRIPTION (provided by applicant): Prostate specific antigen (PSA) screening has vastly improved our ability to identify men at risk of prostate cancer and diagnose this disease at an early stage. But, of men who undergo prostate biopsy due to elevated PSA, only approximately 25% are diagnosed with prostate cancer. For those men with a negative biopsy, the awareness of their risk of prostate cancer has been raised dramatically, and there may be a strong desire to identify methods to reduce their risk of ultimately developing this disease. Many of these men may seek out complementary and alternative medicines (CAM) in an attempt to alter their risk of prostate cancer. A number of CAM compounds, including omega-3 fatty acids (omega-3 FA) and green tea catechins have been hypothesized to reduce prostate cancer risk. However, it is important to understand the biologic mechanism underlying how they may function to slow or inhibit prostate carcinogenesis. One particular biologic pathway, which may be altered by both omega -3 FA and the specific green tea catechin, epigallocatechin-3-gallate (EGCG), is the fatty acid synthase (FAS) pathway. FAS, a lipogenic multienzyme that catalyzes the final step in de novo fatty acid synthesis, has been shown to be highly expressed in prostate carcinogenesis, and has been correlated with greater disease severity. Both EGCG and omega-3 FA have been shown in vitro and in vivo to inhibit this overexpression of FAS. The primary objective or our proposal is to elucidate in men at high risk for prostate cancer, a potential biologic mechanism whereby EGCG, alone or in combination with omega-3 FA, may alter cellular composition and growth, thereby reducing overall risk of prostate cancer. In the proposed GCRC sponsored, randomized, placebo-controlled study we will evaluate the independent and joint effect of EGCG and EGCG plus omega-3 FA on FAS expression, FAS activity, cell proliferation and apoptosis in bengin, pre-neoplastic and neoplastic prostate tissue of men undergoing repeat prostate biopsy. Findings from this study will provide some of the first evidence linking the observed associations between factors modifiable by diet (primarily EGCG and omega-3 FA) and a specific biologic mechanism (FAS pathway) that is suggested to influence prostate carcinogenesis. The elucidation of a single oncogenic pathway that may be regulated by diet may provide a new and exciting opportunity for targeted prevention therapy.