Paclitaxel induces release of cytochrome c from mitochondria isolated from human neuroblastoma cells'.
Paclitaxel is an antimicrotubule agent that induces mitotic block and apoptosis. We show for the first time that paclitaxel acts directly or mitochondria isolated from human cancer cells. In isolated yeast mito chondria, paclitaxel (15 microM) induced an 18% increase in the respiration rate, with no concomitant release of cytochrome c. In isolated neuroblas toma mitochondria, paclitaxel (10-100 microM) induced a 27-72% release o cytochrome c. Release was prevented by cyclosporin A, suggesting the involvement of the permeability transition pore. Doxorubicin did no induce cytochrome c release, whereas vinorelbine, another antimicrotu bule agent, did. Thus, antimicrotubule agents can directly affect mito chondria to induce apoptosis.
André
N
N
UPRESA Centre National de la Recherche Scientifique 6032, Universite de la Mediterranée, Faculty of Pharmacy, Marseille, France.
Braguer
D
D
Brasseur
G
G
Gonçalves
A
A
Lemesle-Meunier
D
D
Guise
S
S
Jordan
M A
MA
Briand
C
C
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D003574:Cytochrome c Group / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D009447:Neuroblastoma / Q000188:drug therapy / Q000201:enzymology* / Q000648:ultrastructure; D010101:Oxygen Consumption / Q000187:drug effects; D017239:Paclitaxel / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000648:ultrastructure; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077235:Vinorelbine
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D003574:Cytochrome c Group; D014747:Vinblastine; D004317:Doxorubicin; D017239:Paclitaxel; D000077235:Vinorelbine