Premium
Procyanidin B3, an inhibitor of histone acetyltransferase, enhances the action of antagonist for prostate cancer cells via inhibition of p300‐dependent acetylation of androgen receptor
Author(s) -
Choi KyungChul,
Yoon HoGeun
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb42
Subject(s) - acetylation , histone acetyltransferase , androgen receptor , prostate cancer , flutamide , chemistry , histone , p300 cbp transcription factors , cell growth , cancer research , epigenetics , biology , histone acetyltransferases , cancer , biochemistry , medicine , gene
Increasing evidence suggests that AR (androgen receptor) acetylation is critical for prostate cancer cell growth. In the present study, we identified Pro‐B3 (procyanidin B3) as a specific HAT (histone acetyltransferase) inhibitor. Pro‐B3 selectively inhibited the activity of HATs, but not other epigenetic enzymes. Pro‐B3 substantially inhibited the p300‐mediated AR acetylation, both in vitro and in vivo. Pro‐B3 inhibited both p300‐dependent and agonist‐induced AR transcription. We demonstrate that the p300‐mediated AR acetylation is critical for the hormone responsiveness of AR. Interestingly, B3 treatment efficiently enhanced the antagonist activity of flutamide through suppression of p300 HAT activity, demonstrating that relative p300 activity is critical for the antagonist action. Finally, Pro‐B3 treatment inhibited acetylation‐dependent prostate cell proliferation and expression of cell‐cycle control genes, subsequently increasing cell death, indicating the functional importance of AR acetylation for prostate cancer cell growth.