Antiandrogenic activity of resveratrol analogs in prostate cancer LNCaP cells.

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Iguchi K, Toyama T, Ito T, Shakui T, Usui S, Oyama M, Iinuma M, Hirano K

Antiandrogenic activity of resveratrol analogs in prostate cancer LNCaP cells.

J Androl. 2012 Nov-Dec;33(6):1208-15. doi: 10.2164/jandrol.112.016782. Epub 2012 Jun 14.

PubMed ID

22700762 [ View in PubMed

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Abstract

The suppression of androgen signaling is a therapeutic target for the treatment of prostate cancer. Resveratrol (3,4',5-trihydroxystilbene) is known to inhibit the function of the androgen receptor (AR). In the present study, we investigated the antiandrogenic activities of resveratrol analogs in order to identify a potent antiandrogen compound. Resveratrol analogs were isolated from plants or were semisynthesized from resveratrol. AR transcriptional activity was measured in prostate cancer LNCaP cells using a luciferase assay with the MMTV-luc reporter plasmid. Among the resveratrol analogs tested, 4'-O-methylresveratrol (3,5-dihydroxy-4'-methoxystilbene) was the most effective inhibitor of AR transcriptional activity. Introduction of a methoxy group to the C-4' of resveratrol and its analogs increased their antiandrogenic activity compared with the unmodified counterparts. Conversely, modification of the 3- and/or 5-hydroxyl groups reduced the antiandrogenic activity. 4'-O-methylresveratrol was more effective than resveratrol in inhibiting Akt phosphorylation, which is related to AR signaling, in LNCaP cells. The hydroxyl groups in resveratrol play a key role in their antiandrogenic effect by modulating AR transcriptional activity.