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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

Authors
 Kyung-Chul CHOI  ;  SiYong PARK  ;  Beom Jin LIM  ;  Ah-Reum SUNG  ;  Yoo-Hyun LEE  ;  Masaki SHIOTA  ;  Akira YOKOMIZO  ;  Seiji NAITO  ;  Younghwa NA  ;  Ho-Geun YOON 
Citation
 Biochemical Journal, Vol.433(1) : 235-244, 2011 
Journal Title
 Biochemical Journal 
ISSN
 0264-6021 
Issue Date
2011
Abstract
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.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/92531
DOI
10.1042/BJ20100980
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부)
Yonsei Authors
윤호근(Yoon, Ho Geun) ; 임범진(Lim, Beom Jin) ; 최경철(Choi, Kyung Chul)
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