Plant flavone apigenin inhibits HDAC and remodels chromatin to induce growth arrest and apoptosis in human prostate cancer cells: In vitro and in vivo study

摘要: Apigenin (4',5,7,-trihydroxyflavone), an anticancer agent, selectively toxic to cancer cells induces cell cycle arrest and apoptosis through mechanisms that have not been fully elucidated. Our studies indicate apigenin-mediated growth inhibitory responses are due inhibition of class I histone deacetylases (HDACs) in prostate cells. Treatment PC-3 22Rv1 with apigenin (20-40 µM) resulted the HDAC enzyme activity, specifically HDAC1 HDAC3 at protein message level. Apigenin-mediated global H3 H4 acetylation, as well localized hyperacetylation on p21/waf1 promoter. A corresponding increase was observed bax mRNA expression after exposure, consistent use inhibitor, trichostatin A. The downstream events demonstrated induction both Studies xenografts athymic nude mice further oral intake doses 20 50 µg/mouse/d over 8-wk period a marked reduction tumor growth, apigenin. An apigenin-fed mice, compared control group. Furthermore, caused significant decrease bcl2 concomitant bax, shifting bax/bcl2 ratio favor apoptosis. findings confirm for first time inhibits HDACs, particularly its exposure results reversal aberrant epigenetic promote malignancy. © 2011 Wiley Periodicals, Inc.