Fish oil, green tea, and prostate cancer prevention.

Abstract

TPS140 Background: Fatty acid synthase (FAS) is a lipogenic multienzyme that catalyzes the final step in de novo fatty acid synthesis. FAS more recently has been characterized as an oncogene and is reported to be overexpressed in several tumor types including prostate. While FAS expression in cancer cells does not appear to be normally regulated by nutritional controls, addition of omega-3 fatty acid (w-3 FA), docosahexanoic acid (DHA) has been shown to inhibit FAS expression and fatty acid production in FAS expressing SK-Br3 human breast cancer cells. Once transcribed, FAS activity is dependent upon the appropriate function of each of its component enzymes. Epigallocatechin- 3-gallate (EGCG), a bioactive compound found in green tea, has been demonstrated to inhibit activity of transcribed FAS in prostate cancer cell lines. The primary objective of our clinical trial is to elucidate, in men at high risk for prostate cancer, a potential biologic mechanism whereby EGCG, alone or in combination with w-3 FA, may alter cellular composition and growth, thereby reducing overall risk of prostate cancer. Methods: In this randomized, placebo-controlled intervention study, subjects are men with an initial negative biopsy considered to be at elevated risk of prostate cancer and scheduled for a repeat biopsy. The primary endpoints of this trial are FAS protein and mRNA expression, as measured by immunohistochemistry (IHC) and real-time (RT)-PCR, FAS activity and cell proliferation (Ki-67 expression) in pre and post- intervention benign, pre-neoplastic and neoplastic prostate tissue. Plasma EGCG and red cell fatty acid concentrations are also measured. Subjects are randomized to green tea, fish oil, green tea+fish oil or double placebo for 12 weeks. Green tea supplements consist of extracted green tea polyphenols (75%) and no less than 30% EGCG (approximately 300 mg) per 1,000 mg capsule. Fish oil capsules (1,000 mg) consist of ethyl esters of eicosapentaenoic acid (20:5n-3) and DHA (22:6 n-3). Men take 2 green tea and 3 fish oil capsules daily for a dose of 1.9g of EPA + DHA and 600 mg EGCG. To date, 67 men have completed the trial and 4 are currently enrolled. Our anticipated sample size is 120 men or 30 men per arm. No significant financial relationships to disclose.