| 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. | |
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MedLine Citation:
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PMID: 22006862 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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 that apigenin-mediated growth inhibitory responses are due to inhibition of class I histone deacetylases (HDACs) in prostate cancer cells. Treatment of PC-3 and 22Rv1 cells with apigenin (20-40 µM) resulted in the inhibition of HDAC enzyme activity, specifically HDAC1 and HDAC3 at the protein and message level. Apigenin-mediated HDAC inhibition resulted in global histone H3 and H4 acetylation, as well as localized hyperacetylation of histone H3 on the p21/waf1 promoter. A corresponding increase was observed in p21/waf1 and bax protein and mRNA expression after apigenin exposure, consistent with the use of HDAC inhibitor, trichostatin A. The downstream events demonstrated cell cycle arrest and induction of apoptosis in both cancer cells. Studies of PC-3 xenografts in athymic nude mice further demonstrated that oral intake of apigenin at doses of 20 and 50 µg/mouse/d over an 8-wk period resulted in a marked reduction in tumor growth, HDAC activity, and HDAC1 and HDAC3 protein expression at both doses of apigenin. An increase in p21/waf1 expression was observed in apigenin-fed mice, compared to the control group. Furthermore, apigenin intake caused a significant decrease in bcl2 expression with concomitant increase in bax, shifting the bax/bcl2 ratio in favor of apoptosis. Our findings confirm for the first time that apigenin inhibits class I HDACs, particularly HDAC1 and HDAC3 and its exposure results in reversal of aberrant epigenetic events that promote malignancy. © 2011 Wiley Periodicals, Inc. |
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Authors:
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Mitali Pandey; Parminder Kaur; Sanjeev Shukla; Ata Abbas; Pingfu Fu; Sanjay Gupta |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-17 |
Journal Detail:
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Title: Molecular carcinogenesis Volume: - ISSN: 1098-2744 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8811105 Medline TA: Mol Carcinog Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Wiley Periodicals, Inc. |
Affiliation:
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Department of Urology, Case Western Reserve University, Cleveland, Ohio. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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