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.

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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