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http://dx.doi.org/10.4062/biomolther.2009.17.1.17

Apicidin Induces Apoptosis via Cytochrome c-Mediated Intrinsic Pathway in Human Ovarian Cancer Cells  

Ahn, Mee-Young (College of Pharmacy, Pusan National University)
Na, Yong-Jin (Department of Obstertrics and Gynecology, College of Medicine, Pusan National University)
Lee, Jae-Won (College of Pharmacy, Pusan National University)
Lee, Byung-Mu (Division of Toxicology, College of Pharmacy, Sungkyunkwan University)
Kim, Hyung-Sik (College of Pharmacy, Pusan National University)
Publication Information
Biomolecules & Therapeutics / v.17, no.1, 2009 , pp. 17-24 More about this Journal
Abstract
Histone deacetylase (HDAC) inhibitors are a promising class of anticancer agents that inhibit cancer cell growth in vitro and in vivo. Previous report has shown that apicidin inhibited SK-OV-3 cells proliferation and down-regulation of cyclin B1 and CDK1, and up-regulation of $p21^{WAF1}$ and p27. However, the mechanism of apicidin-mediated apoptotic cell death is not clearly understood. For this study, we investigated the mechanism of apoptotic pathway induced by apicidin in human ovarian cancer cell. We found that SK-OV-3 cells treated with apicidin caused an increase in the percentage of cells in the G2/M phase, which preceded apoptosis characterized by the appearance of cells with sub-G1 population. To further investigate the mechanism of apoptosis induction by apicidin, we measured TUNEL assay, poly-ADP ribose polymerase (PARP) cleavage, and caspase activity in SK-OV-3 cells treated with apicidin for 48 h. Apicidin significantly enhanced apoptosis as measured by TUNEL positive apoptotic cells, PARP cleavage, and increased Bax/Bcl-2 ratio. Induction of apoptosis was confirmed by the release of cytochrome c to cytosol. Our data suggest that apicidin-induced apoptosis in SK-OV-3 cells was accompanied by caspase-3 activation and the increase in Bax/Bcl-2 ratio. These data suggest that apicidin may be effective in the treatment of ovarian cancer through activation of intrinsic apoptotic pathway.
Keywords
Histone deacetylase inhibitor; Apicidin; Ovarian cancer; Apoptosis;
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