Casein kinase 2 inhibition differentially modulates apoptotic effect of trichostatin A against epithelial ovarian carcinoma cell lines |
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Authors: | Chung Soo Lee Eun-Ra Jang Yun Jeong Kim Soon Chul Myung Wonyong Kim |
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Institution: | 1. Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, 156-756, South Korea 2. Department of Urology, Chung-Ang University Hospital, Seoul, 156-755, South Korea 3. Department of Microbiology, College of Medicine, Chung-Ang University, Seoul, 156-756, South Korea 4. Research Institute for Translational System Bionomics, College of Medicine, Chung-Ang University, Seoul, 156-756, South Korea
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Abstract: | Histone deacetylase inhibitors and casein kinase 2 inhibitors have been shown to induce apoptosis. However, the combined effect of casein kinase 2 inhibition on the apoptotic effect of histone deacetylase inhibitor is unknown. We assessed the effect of casein kinase 2 inhibition on the apoptotic effect of trichostatin A in human epithelial carcinoma cell lines with respect to cell death signaling pathways. At concentrations that did not induce cell death, the casein kinase 2 inhibitor 4,5,6,7-tetrabromobenzotriazole inhibited activation of apoptotic proteins and changes in mitochondrial membrane permeability induced by the histone deacetylase inhibitor trichostatin A. These results suggest that casein kinase 2 inhibition may reduce trichostatin A-induced apoptosis in ovarian carcinoma cell lines by suppressing activation of apoptotic proteins and changes in mitochondrial membrane permeability, which both lead to caspase-3 activation. Casein kinase 2 inhibition, which does not induce a cytotoxic effect, may prevent histone deacetylase inhibitor-mediated apoptosis. |
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