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

FEBS Lett. 2002 Dec 4;532(1-2):256-60. doi: 10.1016/s0014-5793(02)03691-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis*
  • Caspases / metabolism
  • Cell Respiration / drug effects
  • Cytochrome c Group / metabolism
  • Drug Delivery Systems
  • Enzyme Activation
  • Humans
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondria / ultrastructure
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / metabolism
  • Neuroblastoma / ultrastructure
  • Paclitaxel / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Phytogenic
  • Cytochrome c Group
  • Reactive Oxygen Species
  • Caspases
  • Paclitaxel