Protein kinase C inhibition induces apoptosis and ceramide production through activation of a neutral sphingomyelinase

Cancer Res. 1996 Jun 15;56(12):2711-4.


We report that WEHI-231 undergo apoptosis following exposure to the protein kinase C inhibitors chelerythrine chloride and calphostin C. Following the addition of chelerythrine or calphostin C to WEHI-231 cells, ceramide production increased over baseline levels with a concurrent decrease in sphingomyelin. More detailed examinations determined that the ceramide accumulation resulted from activation of neutral, but not acidic, sphingomyelinase. These results suggest an antagonistic relationship between protein kinase C activity and ceramide in the signaling events preceding apoptosis.

Publication types

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

MeSH terms

  • Alkaloids
  • Apoptosis*
  • Benzophenanthridines
  • Cells, Cultured
  • Ceramides / biosynthesis*
  • Hydrolysis
  • Naphthalenes / pharmacology*
  • Phenanthridines / pharmacology*
  • Protein Kinase C / antagonists & inhibitors*
  • Sphingomyelin Phosphodiesterase / metabolism
  • Sphingomyelins / metabolism*


  • Alkaloids
  • Benzophenanthridines
  • Ceramides
  • Naphthalenes
  • Phenanthridines
  • Sphingomyelins
  • chelerythrine
  • Protein Kinase C
  • Sphingomyelin Phosphodiesterase
  • calphostin C