Antiandrogenic activity of resveratrol analogs in prostate cancer LNCaP cells.
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.
Laboratories of Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan.
Kazuhiro
K
Iguchi
Tomoaki
T
Toyama
Tetsuro
T
Ito
Toshinobu
T
Shakui
Shigeyuki
S
Usui
Masayoshi
M
Oyama
Munekazu
M
Iinuma
Kazuyuki
K
Hirano
D000726:Androgen Antagonists / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D010636:Phenols / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011944:Receptors, Androgen / Q000187:drug effects*; D000077185:Resveratrol; D013267:Stilbenes / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
C410798:AR protein, human; D000726:Androgen Antagonists; D010636:Phenols; D011944:Receptors, Androgen; D013267:Stilbenes; D051057:Proto-Oncogene Proteins c-akt; D000077185:Resveratrol