Induction of apoptosis by cancer chemotherapy

Exp Cell Res. 2000 Apr 10;256(1):42-9. doi: 10.1006/excr.2000.4838.


Studies performed over the past five years have demonstrated that there are two major cell-intrinsic pathways for inducing apoptosis, one that begins with ligation of cell surface death receptors and another that involves mitochondrial release of cytochrome c. Several reports have suggested that anticancer drugs kill susceptible cells by inducing expression of death receptor ligands, especially Fas ligand (FasL). Other reports have indicated that chemotherapeutic agents trigger apoptosis by inducing release of cytochrome c from mitochondria. In this review, we describe the two prototypic death pathways, indicate experimental approaches for distinguishing whether chemotherapeutic agents trigger one pathway or the other, summarize current understanding of the role of the two pathways in chemotherapy-induced apoptosis, and discuss the implications of these studies for mechanisms of resistance to chemotherapeutic agents.

Publication types

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

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Agents / toxicity*
  • Apoptosis / drug effects*
  • Cytochrome c Group / metabolism
  • Fas Ligand Protein
  • Humans
  • Membrane Glycoproteins / physiology
  • Mitochondria / drug effects
  • Mitochondria / physiology
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Receptors, Tumor Necrosis Factor / physiology
  • Tumor Cells, Cultured
  • fas Receptor / physiology


  • Antineoplastic Agents
  • Cytochrome c Group
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • Receptors, Tumor Necrosis Factor
  • fas Receptor