title: Paclitaxel targets mitochondria upstream of caspase activation in intact human neuroblastoma cells.
abstract: We previously reported that paclitaxel acted directly on mitochondria isolated from human neuroblastoma SK-N-SH cells. Here, we demonstrate that the direct mitochondrial effect of paclitaxel observed in vitro is relevant in intact SK-N-SH cells. After a 2 h incubation with 1 microM paclitaxel, the mitochondria were less condensed. Paclitaxel (1 microM, 1-4 h) also induced a 20% increase in respiration rate and a caspase-independent production of reactive oxygen species by mitochondria. The paclitaxel-induced release of cytochrome c was detected only after 24 h of incubation, was caspase-independent and permeability transition pore-dependent. Thus, paclitaxel targets mitochondria upstream of caspase activation, early during the apoptotic process in intact human neuroblastoma cells.
authors.affiliation: UMR 6032, University of la Méditerranée, UFR of Pharmacy, 27 Bd Jean Moulin, 13005 Marseille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: André
authors.forename: Manon
authors.initials: M
authors.lastname: Carré
authors.forename: Gaël
authors.initials: G
authors.lastname: Brasseur
authors.forename: Bertrand
authors.initials: B
authors.lastname: Pourroy
authors.forename: Hervé
authors.initials: H
authors.lastname: Kovacic
authors.forename: Claudette
authors.initials: C
authors.lastname: Briand
authors.forename: Diane
authors.initials: D
authors.lastname: Braguer
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D019069:Cell Respiration / Q000187:drug effects; D003574:Cytochrome c Group / Q000378:metabolism; D016503:Drug Delivery Systems; D004789:Enzyme Activation; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000648:ultrastructure; D017239:Paclitaxel / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003574:Cytochrome c Group; D017382:Reactive Oxygen Species; D020169:Caspases; D017239:Paclitaxel