A lysosomal-mitochondrial death pathway is induced by solamargine in human K562 leukemia cells.
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 2h 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 Ca(2+) overload is more pronounced in SM-treated cells. Cells exposed to 10 microM 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.
Sun
Lingmei
L
School of Pharmaceutical Sciences, Shandong University, Jinan, China.
Zhao
Ying
Y
Li
Xia
X
Yuan
Huiqing
H
Cheng
Aixia
A
Lou
Hongxiang
H
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008247:Lysosomes / Q000187:drug effects* / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D051336:Mitochondrial Membranes / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012991:Solanaceous Alkaloids / Q000494:pharmacology*; D014410:Tumor Stem Cell Assay; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012991:Solanaceous Alkaloids; D051028:bcl-2-Associated X Protein; C026609:beta-solamarine; D020169:Caspases; D002401:Cathepsin B; D002118:Calcium