Resveratrol down-regulates the androgen receptor at the post-translational level in prostate cancer cells.
Androgen receptor (AR) functions as a transcriptional factor for the development and progression of prostate cancer. Resveratrol is known to inhibit the function of AR and to repress AR expression at the transcriptional level. This study focuses on the effects of resveratrol on the AR function and the post-translational AR level. Resveratrol repressed the transcriptional activities of a mutant AR lacking the ligand-binding domain, a constitutive active form of AR, and wild-type AR in a concentration-dependent manner in human prostate cancer PC-3 cells, indicating that resveratrol does not inhibit the transcriptional activity of AR through binding to the ligand-binding domain of AR. Furthermore, the half-life of AR protein was approximately 4 h in resveratrol-treated AR-positive prostate cancer LNCaP cells, compared to approximately 13 h in control cells, as determined by cycloheximide chase. These results indicate that resveratrol down-regulates AR protein through a post-translational mechanism and suggest that the inhibitory effect of resveratrol on AR function is partly attributable to a decrease in the post-translational AR level.
Harada
Naoki
N
Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan.
Murata
Yohei
Y
Yamaji
Ryoichi
R
Miura
Takumi
T
Inui
Hiroshi
H
Nakano
Yoshihisa
Y
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D011944:Receptors, Androgen / Q000235:genetics*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D011944:Receptors, Androgen; D013267:Stilbenes; D000077185:Resveratrol