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Abstract Title:

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

Abstract Source:

J Steroid Biochem Mol Biol. 2011 Jan;123(1-2):65-70. Epub 2010 Nov 10. PMID: 21073951

Abstract Author(s):

Naoki Harada, Kiyotaka Atarashi, Yohei Murata, Ryoichi Yamaji, Yoshihisa Nakano, Hiroshi Inui

Article Affiliation:

Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 5998531, Japan.

Abstract:

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 24h, 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 10μM resveratrol for 3h, 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 (24h) 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 thenucleus.

Study Type : In Vitro Study

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Sayer Ji
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