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.
|
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 |
Journal | Journal of medicinal food
(J Med Food)
2011 Jan-Feb
Vol. 14
Issue 1-2
Pg. 9-16
ISSN: 1557-7600 [Electronic] United States |
PMID | 21244239
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Grape Seed Extract
- Receptors, Androgen
- Histone Acetyltransferases
|
Topics |
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Gene Expression Regulation, Neoplastic
(drug effects)
- Grape Seed Extract
(pharmacology, therapeutic use)
- Histone Acetyltransferases
(antagonists & inhibitors, genetics, metabolism)
- Humans
- Male
- Prostatic Neoplasms
(drug therapy, enzymology, genetics, physiopathology)
- Receptors, Androgen
(genetics, metabolism)
- Transcription, Genetic
(drug effects)
|