Journal
TOXICOLOGY IN VITRO
Volume 24, Issue 6, Pages 1504-1511Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2010.07.013
Keywords
Lysosome; Cathepsin B; Mitochondria; Cytochrome c; Apoptosis
Categories
Funding
- National Natural Science Foundation of China [30925038]
- Shandong Provincial Foundation [2006GG1102023, BS2009YY016]
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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. (C) 2010 Elsevier Ltd. All rights reserved.
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