Implication of mitochondria-derived ROS and cardiolipin peroxidation in N-(4-hydroxyphenyl)retinamide-induced apoptosis

Br J Cancer. 2002 Jun 17;86(12):1951-6. doi: 10.1038/sj.bjc.6600356.

Abstract

We have studied the effect of N-(4-hydroxyphenyl)retinamide on either malignant human leukaemia cells or normal cells and investigated its mechanism of action. We demonstrate that 4HPR induces reactive oxygen species increase on mitochondria at a target between mitochondrial respiratory chain complex I and II. Such oxidative stress causes cardiolipin peroxidation which in turn allows cytochrome c release to cytosol, caspase-3 activation and therefore apoptotic consumption. Moreover, this apoptotic pathway seems to be bcl-2/bax independent and count only on malignant cells but not normal nor activated lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cardiolipins / metabolism*
  • Fenretinide / pharmacology*
  • Humans
  • Lipid Peroxidation / drug effects*
  • Mitochondria / drug effects*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • Reactive Oxygen Species / metabolism*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Cardiolipins
  • Reactive Oxygen Species
  • Fenretinide