Nitroxide TEMPOL impairs mitochondrial function and induces apoptosis in HL60 cells

J Cell Biochem. 2001;82(2):271-6. doi: 10.1002/jcb.1160.

Abstract

The piperidine nitroxide TEMPOL induces apoptosis in a number of tumor cell lines through free radical-dependent mechanisms. As mitochondria play a major role in apoptosis as both source and target for free radicals, the present study focuses on mitochondrial effects of TEMPOL in a human promyelocytic leukemic cell line (HL-60). On 24-h exposure to TEMPOL, the following alterations were observed: 1) decrease in both the intracellular and mitochondrial glutathione pools; 2) impairment of oxidative phosphorylation; and 3) decrease in mitochondrial membrane potential. In addition, TEMPOL was found to specifically target complex I of the respiratory chain, with minor effects on complexes II and IV, suggesting that mitochondrial effects might play a role in TEMPOL-induced oxidative stress and apoptosis, and that TEMPOL might sensitize tumor cells to the pro-apoptotic effects of cytotoxic agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Chromatography, High Pressure Liquid
  • Cyclic N-Oxides / pharmacology*
  • Electron Transport Complex II
  • Electron Transport Complex III / antagonists & inhibitors
  • Electron Transport Complex IV / antagonists & inhibitors
  • Enzyme Inhibitors / pharmacology
  • Glutathione / metabolism
  • HL-60 Cells / cytology
  • HL-60 Cells / drug effects*
  • Humans
  • Intracellular Membranes / drug effects
  • Membrane Potentials / drug effects
  • Mitochondria / drug effects*
  • Multienzyme Complexes / antagonists & inhibitors
  • Neoplasm Proteins / antagonists & inhibitors
  • Oxidation-Reduction
  • Oxidative Phosphorylation / drug effects
  • Oxidoreductases / antagonists & inhibitors
  • Rotenone / pharmacology
  • Sodium Azide / pharmacology
  • Spin Labels
  • Succinate Dehydrogenase / antagonists & inhibitors

Substances

  • Antioxidants
  • Cyclic N-Oxides
  • Enzyme Inhibitors
  • Multienzyme Complexes
  • Neoplasm Proteins
  • Spin Labels
  • Rotenone
  • Sodium Azide
  • Oxidoreductases
  • Electron Transport Complex II
  • Succinate Dehydrogenase
  • Electron Transport Complex IV
  • Electron Transport Complex III
  • Glutathione
  • tempol