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Effect of anti‐histone acetyltransferase activity from Ephedrae Radix extracts on androgen receptor‐mediated transcriptional regulation
Author(s) -
Kim HanCheon,
Lee YooHyun,
Yoo JungYoon,
Yoon HoGeun
Publication year - 2008
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.22.2_supplement.204
Subject(s) - histone acetyltransferase , lncap , acetylation , histone , histone deacetylase , androgen receptor , chemistry , histone acetyltransferases , epigenetics , hdac4 , cancer research , pharmacology , biochemistry , prostate cancer , biology , cancer , gene , genetics
Histone acetylation, regulated by histone acetyltransferases (HATs) and deacetylases (HDACs), is an epigenetic mechanism that influences eukaryotic transcription. Significant changes in histone acetylation are associated with cancer. Thus, manipulating acetylation status of key gene targets is likely to be crucial for effective cancer therapy. While specific histone deacetylase inhibitors exist there are few effective HAT inhibitors identified. Towards this end, we screened plant extracts to identify potent HAT inhibitors. Ephedrae Radix ethanol extract inhibited both p300 and CBP (60–70% at 100 μg/ml) activity. We show Ephedrae Radix ethanol extract mediates agonist‐dependent androgen receptor (AR) activation and suppresses antagonist‐dependent inhibition. Ephedrae Radix ethanol extract treatment also decreased transcription of AR regulated genes and also reduced histone H3 and AR acetylation in the promoters of prostate specific antigen (PSA) and β‐2‐microglobulin (B2M). Finally, Ephedrae Radix ethanol extract treatment reduced the growth of LNCaP, a human prostate cancer cell line. These results demonstrate Ephedrae Radix ethanol extract is a potent HAT inhibitor, which reduced AR and histone acetylation leading to decreased AR mediated transcription and reduced LNCaP cell growth. This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea gorvenment (MOST) (No. R13‐2002‐054‐04002‐0); a grant (code #20070301034007) from BioGreen 21 program, Rural Development Administration, Republic of Korea.