Effects of docosahexaenoic acid and eicosapentaenoic acid on androgen-mediated cell growth and gene expression in LNCaP prostate cancer cells

There is some epidemiological support for a protective influence of omega - 3 fatty acids against prostate cancer. We wanted to explore whether omega - 3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and eicosa pentaenoic acid (EPA) can affect androgen receptor function in prostate can cer cells. Our study showed that both DHA and EPA inhibit androgen-stimulat ed cell growth. Androgenic induction of prostate-specific antigen (PSA) pro tein was repressed by DHA and EPA in a dose-dependent manner. The mRNA leve ls of five androgen up-regulated genes, PSA, ornithine decarboxylase, NKX 3 .1, immunophilin fkbp 51 and Drg-1, were decreased with DHA treatment in th e presence of androgens. Transfection experiments using a DNA vector contai ning androgen-responsive elements demonstrated that both DHA and EPA could interfere with transactivation activities of the androgen receptor (AR). Ho wever, western blot analysis of AR protein showed that DHA and EPA treatmen ts did not change AR expression levels. Interestingly, the proto-oncoprotei n e-jun was increased by DHA treatment. A transient transfection found that forced expression of e-jun inhibited AR transactivation activity. Thus, th is study found that the inhibitory effects of omega -3 polyunsaturated fatt y acids on AR-mediated actions are due, at least in part, to an increase in c-jun protein.