Apoptotic activities of C2-ceramide and C2-dihydroceramide homologues against HL-60 cells

Bioorg Med Chem. 2003 Jul 3;11(13):2723-8. doi: 10.1016/s0968-0896(03)00228-1.

Abstract

The apoptotic activities of non-natural ceramide homologues, C2-homo-ceramide, C2-homo-dihydroceramide, C2-bishomo-ceramide and C2-bishomo-dihydroceramide, were examined using human leukemia HL-60 cells. The apoptotic activity was in order of C2-ceramide>C2-homo-ceramide approximately C2-bishomo-ceramide and the activities of the L-erythro- and D-erythro-ceramide homologues were similar. The morphological features of the cells, DNA fragmentations, proteolytic processing of pro-caspase-3 and the cleavage of PARP as the result of treatments with these homologues indicated that cell death was induced by apoptosis.

MeSH terms

  • Apoptosis / drug effects*
  • Caspase 3
  • Caspases / analysis
  • Ceramides / chemical synthesis
  • Ceramides / pharmacology*
  • DNA Fragmentation
  • Dose-Response Relationship, Drug
  • HL-60 Cells
  • Humans
  • Kinetics
  • Poly Adenosine Diphosphate Ribose / metabolism
  • Sphingosine / analogs & derivatives*
  • Structure-Activity Relationship

Substances

  • Ceramides
  • N-acetylsphingosine
  • dihydroceramide
  • Poly Adenosine Diphosphate Ribose
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Sphingosine