Journal Article

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 and Charles Y. F. Young

in Carcinogenesis

Volume 22, issue 8, pages 1201-1206
Published in print August 2001 | ISSN: 0143-3334
Published online August 2001 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/22.8.1201
Effects of docosahexaenoic acid and eicosapentaenoic acid on androgen-mediated cell growth and gene expression in LNCaP prostate cancer cells

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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.

Keywords: AR, androgen receptor; ARE, androgen-responsive element; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; FBS, fetal bovine serum; β-gal, β-galactosidase; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; Mib, mibolerone; ODC, ornithine decarboxylase; PSA, prostate-specific antigen.

Journal Article.  4569 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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