BACKGROUND: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 anti-androgenic activities of resveratrol analogs in order to identify a potent anti-androgen compound.
METHODS:Resveratrol analogs were isolated from plants or were semi-synthesized from resveratrol. AR transcriptional activity was measured in prostate cancer LNCaP cells using a luciferase assay with the MMTV-luc reporter plasmid.
RESULTS: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 anti-androgenic activity compared to the unmodified counterparts. Conversely, modification of the 3- and/or 5-hydroxyl groups reduced the anti-androgenic activity. 4'-O-methylresveratrol was more effective than resveratrol in inhibiting Akt phosphorylation, which is related to androgen receptor signaling, in LNCaP cells.
CONCLUSIONS: The hydroxyl groups in resveratrol play a key role in their anti-androgenic effect by modulating AR transcriptional activity.
Written by:
Iguchi K, Toyama T, Ito T, Shakui T, Usui S, Oyama M, Iinuma M, Hirano K. Are you the author?
Reference: J Androl. 2012 Jun 14. Epub ahead of print.
doi: 10.2164/jandrol.112.016782
PubMed Abstract
PMID: 22700762
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