Superoxide anion is a natural inhibitor of FAS-mediated cell death

EMBO J. 1996 Jan 15;15(2):216-25.


The cell surface receptor Fas is a major trigger of apoptosis. However, expression of the Fas receptor in many tumor cell types does not correlate with sensitivity to Fas-mediated cell death. Because a prooxidant state is a common feature of tumor cells, we examined the role of intracellular reactive oxygen intermediates in the regulation of Fas-mediated cytotoxicity. Our results show that an oxidative stress induced by increasing the intracellular superoxide anion (O2-) concentration can abrogate Fas-mediated apoptosis in cells which are constitutively sensitive to Fas. Conversely, an O2- concentration decrease is observed to sensitize cells which are naturally resistant to Fas signals. These observations suggest that intracellular O2- may play a key role in regulating cell sensitivity to a potentially lethal signal and provide tumor cells with a natural, inducible mechanism of resistance to Fas-mediated apoptosis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antioxidants / pharmacology*
  • Apoptosis* / drug effects
  • Bone Neoplasms
  • Cell Line
  • Ditiocarb / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Kinetics
  • Luminescent Measurements
  • Melanoma
  • Osteosarcoma
  • Oxidative Stress
  • Phorbol Esters / pharmacology*
  • Reactive Oxygen Species / pharmacology
  • Recombinant Proteins / biosynthesis
  • Superoxides / metabolism*
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / physiology
  • Urinary Bladder Neoplasms
  • fas Receptor / biosynthesis
  • fas Receptor / physiology*


  • Antioxidants
  • Enzyme Inhibitors
  • Phorbol Esters
  • Reactive Oxygen Species
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • Superoxides
  • Ditiocarb