Programmed cell death induced by ceramide

Science. 1993 Mar 19;259(5102):1769-71. doi: 10.1126/science.8456305.


Sphingomyelin hydrolysis and ceramide generation have been implicated in a signal transduction pathway that mediates the effects of tumor necrosis factor-alpha (TNF-alpha) and other agents on cell growth and differentiation. In many leukemic cells, TNF-alpha causes DNA fragmentation, which leads to programmed cell death (apoptosis). C2-ceramide (0.6 to 5 microM), a synthetic cell-permeable ceramide analog, induced internucleosomal DNA fragmentation, which was inhibited by zinc ion. Other amphiphilic lipids failed to induce apoptosis. The closely related C2-dihydroceramide was also ineffective, which suggests a critical role for the sphingolipid double bond. The effects of C2-ceramide on DNA fragmentation were prevented by the protein kinase C activator phorbol 12-myristate 13-acetate, which suggests the existence of two opposing intracellular pathways in the regulation of apoptosis.

Publication types

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

MeSH terms

  • Apoptosis / drug effects*
  • Ceramides / pharmacology*
  • DNA / metabolism
  • DNA Damage
  • Leukemia
  • Nucleosomes / drug effects
  • Nucleosomes / metabolism
  • Protein Kinase C / metabolism
  • Sphingomyelins / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology
  • Zinc / pharmacology


  • Ceramides
  • Nucleosomes
  • Sphingomyelins
  • Tumor Necrosis Factor-alpha
  • DNA
  • Protein Kinase C
  • Zinc
  • Tetradecanoylphorbol Acetate