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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 ; Ho-Geun Yoon ; Han-Joon Hwang ; Ok-Hee Lee ; Hyo-Kyoung Choi ; Ah-Reum Seong ; Kyung-Chul Choi 
Citation
 Journal of Medicinal Food, Vol.14(1-2) : 9~16, 2011 
Journal Title
 Journal of Medicinal Food 
ISSN
 1096-620X 
Issue Date
2011
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.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/92851
DOI
10.1089/jmf.2010.1264
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Biochemistry & Molecular Biology
1. 연구논문 > 1. College of Medicine > Dept. of Life Science
1. 연구논문 > 5. Research Institutes > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease
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Link
 http://online.liebertpub.com/doi/abs/10.1089/jmf.2010.1264
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