The topoisomerase inhibitors camptothecin and etoposide induce a CD95-independent apoptosis of activated peripheral lymphocytes

Cell Death Differ. 2000 Feb;7(2):197-206. doi: 10.1038/sj.cdd.4400595.


The effect of etoposide and camptothecin, two topoisomerase inhibitors directed against topoisomerases II and I, respectively, was evaluated on human peripheral blood lymphocytes. Etoposide and camptothecin induced apoptosis of mitogen-activated but not resting CD4+ and CD8+ T lymphocytes. Cell sensitivity to these agents required G1 to S-phase transition of the cell cycle. Conversely, daunorubicin, an intercalating agent and topoisomerase II inhibitor, induced apoptosis of both resting and activated lymphocytes. Although etoposide and camptothecin induced CD95-ligand mRNA expression, drug-induced apoptosis of activated human lymphocytes was not inhibited by CD95 antagonists. Drug-induced cell death was also not inhibited by p55 TNFR-Ig fusion protein. Activation of the caspases cascade was suggested by the partial inhibitory effect of the tripeptide zVAD-fmk and documented by activation of caspase 3. Finally etoposide and camptothecin induced a rapid production of ceramide in activated but not resting peripheral blood lymphocytes, suggesting that ceramide might initiate the signaling apoptotic cascade in sensitive cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Camptothecin / pharmacology*
  • Cells, Cultured
  • DNA Topoisomerases, Type I / metabolism*
  • Enzyme Inhibitors / pharmacology*
  • Etoposide / pharmacology*
  • Humans
  • Lymphocyte Activation
  • Lymphocytes / pathology*
  • Nucleic Acid Synthesis Inhibitors / pharmacology*
  • Signal Transduction / drug effects
  • Topoisomerase I Inhibitors
  • fas Receptor


  • Enzyme Inhibitors
  • Nucleic Acid Synthesis Inhibitors
  • Topoisomerase I Inhibitors
  • fas Receptor
  • Etoposide
  • DNA Topoisomerases, Type I
  • Camptothecin