Aspirin induces apoptosis through mitochondrial cytochrome c release.
Aspirin and other non-steroidal anti-inflammatory drugs induce apoptosis in many cell types. Although the involvement of caspases has been demonstrated, the mechanism leading to caspase activation remains unknown. We have studied the role of the mitochondrial pathway in aspirin-induced apoptosis. The apoptotic effect of aspirin was analyzed in different cell lines (Jurkat, MOLT-4, Raji and HL-60) showing induction of mitochondrial cytochrome c release and caspases 9, 3 and 8 processing. Furthermore, early aspirin-induced cytochrome c release was not affected by the caspase inhibitor Z-VAD x fmk and preceded loss of mitochondrial membrane potential. Therefore, aspirin-induced apoptosis involves caspase activation through cytochrome c release.
Piqué
M
M
Departament de Ciències Fisiològiques II, Universitat de Barcelona, L'Hospitalet, Spain.
Barragán
M
M
Dalmau
M
M
Bellosillo
B
B
Pons
G
G
Gil
J
J
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis; D001241:Aspirin / Q000494:pharmacology*; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism*; D004789:Enzyme Activation; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011499:Protein Processing, Post-Translational; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003574:Cytochrome c Group; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D001241:Aspirin