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Paclitaxel targets mitochondria upstream of caspase activation in intact human neuroblastoma cells
Author(s) -
André Nicolas,
Carré Ma,
Brasseur Gaël,
Pourroy Bertrand,
Kovacic Hervé,
Briand Claudette,
Braguer Diane
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03691-8
Subject(s) - paclitaxel , mitochondrion , apoptosis , cytochrome c , incubation , mitochondrial permeability transition pore , chemistry , caspase 3 , reactive oxygen species , neuroblastoma , microbiology and biotechnology , in vitro , caspase 9 , biology , biochemistry , cell culture , programmed cell death , chemotherapy , genetics
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 μM paclitaxel, the mitochondria were less condensed. Paclitaxel (1 μM, 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.