A lysosomal-mitochondrial death pathway is induced by solamargine in human K562 leukemia cells

作者：Sun, Lingmei; Zhao, Ying; Li, Xia; Yuan, Huiqing; Cheng, Aixia; Lou, Hongxiang^*

来源：Toxicology in Vitro, 2010, 24(6): 1504-1511.

DOI：10.1016/j.tiv.2010.07.013

• Lysosome
• Cathepsin B
• Mitochondria
• Cytochrome c
• Apoptosis

Solamargine (SM), a steroidal alkaloid glycoside from Solanum nigrum L, displayed a superior cytotoxicity to many human tumor cells. Further investigation with human K562 leukemia cells found that SM could induce an early lysosomal rupture within 2 h as assessed by acridine-orange relocation and alkalinization of lysosomes. Intracellular lysosomal rupture is also confirmed with the release of cathepsin B to cytosol detected by western blot. Subsequent mitochondrial damage including mitochondrial membrane permeabilization detected by decrease membrane potential as well as the release of cytochrome c from mitochondria was also observed. The cellular Ca2+ overload is more pronounced in SM-treated cells. Cells exposed to 10 mu M SM for 30 min showed a maximum 7-fold increase in intracellular calcium concentration compared with vehicle-treated controls. The down-expression of Bcl-2, up-regulation of Bax, caspase-3 and caspase-9 activities followed by above changes revealed that the cytotoxicity of SM was involved in a lysosomal-mitochondrial death pathway induced by SM.

• 出版日期2010-9
• 单位山东大学