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

Byung Ha Chung, Susan H. Mitchell, Jin San Zhang, Charles Y.F. Young

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

Abstract

There is some epidemiological support for a protective influence of ω-3 fatty acids against prostate cancer. We wanted to explore whether ω-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) can affect androgen receptor function in prostate cancer cells. Our study showed that both DHA and EPA inhibit androgen-stimulated cell growth. Androgenic induction of prostate-specific antigen (PSA) protein was repressed by DHA and EPA in a dose-dependent manner. The mRNA levels of five androgen up-regulated genes, PSA, ornithine decarboxylase, NKX 3.1, immunophilin fkbp 51 and Drg-1, were decreased with DHA treatment in the presence of androgens. Transfection experiments using a DNA vector containing androgen-responsive elements demonstrated that both DHA and EPA could interfere with transactivation activities of the androgen receptor (AR). However, western blot analysis of AR protein showed that DHA and EPA treatments did not change AR expression levels. Interestingly, the proto-oncoprotein c-jun was increased by DHA treatment. A transient transfection found that forced expression of c-jun inhibited AR transactivation activity. Thus, this study found that the inhibitory effects of ω-3 polyunsaturated fatty acids on AR-mediated actions are due, at least in part, to an increase in c-jun protein.

Original languageEnglish
Pages (from-to)1201-1206
Number of pages6
JournalCarcinogenesis
Volume22
Issue number8
DOIs
Publication statusPublished - 2001

All Science Journal Classification (ASJC) codes

  • Cancer Research

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