Inhibitory mechanisms of the transcriptional activity of androgen receptor by resveratrol: Implication of DNA binding and acetylation of the receptor

Androgen receptor (AR) is a ligand-dependent transcription factor and plays a key role in the development of prostate cancer. Resveratrol, a polyphenolic compound, inhibits AR function and reduces the level of prostate-specific antigen (PSA), a notable target gene of AR. Here, we investigated the mechanisms by which resveratrol inhibits AR function. Although the protein levels of AR were decreased by resveratrol treatment for 24 h, the decrease could not fully account for the suppression of AR function. The total and the nuclear AR levels were not affected after incubation with 10 μM resveratrol for 3 h, whereas resveratrol inhibited the binding of AR to the enhancer region of PSA and decreased the acetylation of AR even at this early phase. Inhibition of transcription by resveratrol was weaker in the AR acetylation site mutant than in the wild-type. In later phase (24 h) after incubation with resveratrol, the ligand-induced nuclear accumulation of AR was markedly decreased by resveratrol. These data show that resveratrol inhibits DNA binding of AR, presumably by decreasing its level of acetylation and suggest that acetylation of AR is involved in its accumulation in the nucleus.

Research highlights▶ Resveratrol caused a greater decrease in PSA than in androgen receptor. ▶ Resveratrol inhibited the binding of androgen receptor to the enhancer region of PSA. ▶ Resveratrol decreased the acetylation of androgen receptor.