Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea.
Mol Cell Biochem. 2010 May;338(1-2):157-66. doi: 10.1007/s11010-009-0349-1. Epub 2009 Dec 18.
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.
组蛋白去乙酰化酶抑制剂和酪蛋白激酶 2 抑制剂已被证明可诱导细胞凋亡。然而，酪蛋白激酶 2 抑制对组蛋白去乙酰化酶抑制剂诱导的细胞凋亡的协同作用尚不清楚。我们评估了酪蛋白激酶 2 抑制剂对人类上皮癌细胞系中曲古抑菌素 A 的细胞凋亡作用的影响，涉及细胞死亡信号通路。在不诱导细胞死亡的浓度下，酪蛋白激酶 2 抑制剂 4,5,6,7-四溴苯并三唑抑制了组蛋白去乙酰化酶抑制剂曲古抑菌素 A 诱导的凋亡蛋白的激活和线粒体膜通透性的改变。这些结果表明，酪蛋白激酶 2 抑制可能通过抑制凋亡蛋白的激活和线粒体膜通透性的改变来减少卵巢癌细胞系中曲古抑菌素 A 诱导的细胞凋亡，这两者都导致 caspase-3 的激活。不会诱导细胞毒性作用的酪蛋白激酶 2 抑制可能会阻止组蛋白去乙酰化酶抑制剂介导的细胞凋亡。
