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Updated: Jul 8, 2026

An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Resveratrol down-regulates the androgen receptor at the post-translational level in prostate cancer cells
Naoki Harada1, Yohei Murata, Ryoichi Yamaji
1Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan.
Abstract:
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.
Insights
Resveratrol inhibits prostate cancer progression by reducing androgen receptor (AR) levels. This study shows resveratrol decreases AR protein stability, impacting its function through post-translational mechanisms.
Area of Science:
- Molecular Biology
- Oncology
- Nutraceuticals
Background:
- Androgen receptor (AR) is a key factor in prostate cancer development and progression.
- Resveratrol is known to inhibit AR function and expression transcriptionally.
Purpose of the Study:
- To investigate the effects of resveratrol on AR function and post-translational AR levels.
- To elucidate the mechanism by which resveratrol impacts AR activity in prostate cancer cells.
Main Methods:
- Assessed resveratrol's effect on wild-type and mutant AR transcriptional activity in PC-3 cells.
- Determined AR protein half-life using cycloheximide chase in LNCaP cells with and without resveratrol.
Main Results:
- Resveratrol repressed AR transcriptional activity independently of the ligand-binding domain.
- Resveratrol significantly reduced AR protein half-life from approximately 13 h to 4 h.
- This indicates resveratrol down-regulates AR protein via a post-translational mechanism.
Conclusions:
- Resveratrol inhibits AR function partly by decreasing post-translational AR protein levels.
- The findings suggest a novel therapeutic strategy for prostate cancer utilizing resveratrol.
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