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Grape seed extract regulates androgen receptor-mediated transcription in prostate cancer cells through potent anti-histone acetyltransferase activity.

Authors
 Si Yong Park  ;  Yoo-Hyun Lee  ;  Kyung-Chul Choi  ;  Ah-Reum Seong  ;  Hyo-Kyoung Choi  ;  Ok-Hee Lee  ;  Han-Joon Hwang  ;  Ho-Geun Yoon 
Citation
 JOURNAL OF MEDICINAL FOOD, Vol.14(1-2) : 9-16, 2011 
Journal Title
 JOURNAL OF MEDICINAL FOOD 
ISSN
 1096-620X 
Issue Date
2011
MeSH
Cell Line, Tumor ; Cell Proliferation/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Grape Seed Extract/pharmacology* ; Grape Seed Extract/therapeutic use* ; Histone Acetyltransferases/antagonists & inhibitors* ; Histone Acetyltransferases/genetics ; Histone Acetyltransferases/metabolism ; Humans ; Male ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/enzymology* ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/physiopathology ; Receptors, Androgen/genetics ; Receptors, Androgen/metabolism* ; Transcription, Genetic/drug effects*
Abstract
Histone acetylation, which is regulated by histone acetyltransferases (HATs) and deacetylases, is an epigenetic mechanism that influences eukaryotic transcription. Significant changes in histone acetylation are associated with cancer; therefore, manipulating the acetylation status of key gene targets is likely crucial for effective cancer therapy. Grape seed extract (GSE) has a known protective effect against prostate cancer. Here, we showed that GSE significantly inhibited HAT activity by 30-80% in vitro (P < .05). Furthermore, we demonstrated significant repression of androgen receptor (AR)-mediated transcription by GSE in prostate cancer cells by measuring luciferase activity using a pGL3-PSA construct bearing the AR element in the human prostate cancer cell line LNCaP (P < .05). GSE treatment also decreased the mRNA level of the AR-regulated genes PSA and NKX 3.1. Finally, GSE inhibited growth of LNCaP cells. These results indicate that GSE potently inhibits HAT, leading to decreased AR-mediated transcription and cancer cell growth, and implicate GSE as a novel candidate for therapeutic activity against prostate cancer.
Full Text
http://online.liebertpub.com/doi/abs/10.1089/jmf.2010.1264
DOI
10.1089/jmf.2010.1264
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
5. Research Institutes (연구소) > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease (뇌심혈관질환융합연구사업단) > 1. Journal Papers
Yonsei Authors
Yoon, Ho Geun(윤호근) ORCID logo https://orcid.org/0000-0003-2718-3372
Lee, Ok Hee(이옥희)
Choi, Kyung Chul(최경철)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/92851
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