Paclitaxel targets mitochondria upstream of caspase activation in intact human neuroblastoma cells

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 muM paclitaxel, the mitochondria were less condensed. Paclitaxel (1 muM, 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. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.