Arimochi Hideki, Morita Kyoji
Department of Molecular Bacteriology, Tokushima University School of Medicine, Tokushima, Japan.
Pharmacology. 2008;81(2):164-72. doi: 10.1159/000111144. Epub 2007 Nov 19.
Cytotoxic effects of desipramine on human colon carcinoma HT29 and HCT116 cells were examined. Desipramine reduced the viability of HT29 cells in a concentration-dependent manner, but failed to cause any significant change in the viability of HCT116 cells by the concentration up to 50 mumol/l, at which an approximately 60% reduction of the viability of HT29 cells was observed. Despite their different sensitivities, desipramine caused the nonoxidative apoptotic damage to both of them. In contrast to HT29 cells, desipramine might cause the apoptotic death of HCT116 cells through the disturbance of mitochondrial function. These results suggest that desipramine may cause the nonoxidative apoptotic damage to different types of human colon carcinoma cells through either a nonmitochondrial or a mitochondrial pathway, which may confer the different sensitivities to this drug on these tumor cells.
检测了去甲丙咪嗪对人结肠癌HT29和HCT116细胞的细胞毒性作用。去甲丙咪嗪以浓度依赖性方式降低HT29细胞的活力，但在浓度高达50μmol/L时，未能引起HCT116细胞活力的任何显著变化，此时观察到HT29细胞活力降低约60%。尽管它们的敏感性不同，去甲丙咪嗪对两者均造成了非氧化性凋亡损伤。与HT29细胞相反，去甲丙咪嗪可能通过干扰线粒体功能导致HCT116细胞凋亡死亡。这些结果表明，去甲丙咪嗪可能通过非线粒体或线粒体途径对不同类型的人结肠癌细胞造成非氧化性凋亡损伤，这可能赋予这些肿瘤细胞对该药物不同的敏感性。
