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 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 omega-3 polyunsaturated fatty acids on AR-mediated actions are due, at least in part, to an increase in c-jun protein.
Chung
B H
BH
Department of Urology and Department of Biochemistry and Molecular Biology, Mayo Foundation, Guggenheim Building 1742B, 200 First Street SW, Rochester, MN 55905, USA.
Mitchell
S H
SH
Zhang
J S
JS
Young
C Y
CY
D059002:Androgen Receptor Antagonists; D000728:Androgens / Q000502:physiology*; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D059002:Androgen Receptor Antagonists; D000728:Androgens; D012333:RNA, Messenger; D011944:Receptors, Androgen; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid