Molecular mechanism of staurosporine-induced apoptosis in osteoblasts

Pharmacol Res. 2000 Oct;42(4):373-81. doi: 10.1006/phrs.2000.0700.


Staurosporine, a microbial alkaloid, is a strong inhibitor of protein kinases. We induced apoptosis in murine osteoblast MC3T3E-1 cells by exposure to the staurosporine. Staurosporine transiently increased the phosphotransferase activity of c-Jun N-terminal kinase-1 (JNK1), which in turn may activate the transcriptional activity of activating protein-1 (AP-1). We then prepared extracts from staurosporine-treated MC3T3E-1 cells and monitored the cleavage of acetyl-YVAD-AMC and acetyl-DEVD-AMC, fluorogenic substrates of caspase-1-like and caspase-3-like proteases, respectively. Staurosporine caused a significant increase in the proteolytic activity of caspase-3-like proteases, but not in the activity of caspase-1-like proteases. Furthermore, staurosporine increased the transcriptional activity of nuclear factor- kappa B (NF- kappa B). These data suggest that staurosporine-induced apoptosis in osteoblasts may occur via activation of JNK1, caspase-3-like proteases, and transcriptional factors including AP-1 and NF- kappa B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Apoptosis*
  • Caspase 3
  • Caspases / chemistry
  • Endopeptidases / metabolism
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Mice
  • Mitogen-Activated Protein Kinase 8
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Osteoblasts / drug effects*
  • Osteoblasts / enzymology
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • Phosphotransferases / metabolism
  • Staurosporine / pharmacology*
  • Transcription Factor AP-1 / metabolism


  • Enzyme Inhibitors
  • NF-kappa B
  • Transcription Factor AP-1
  • Phosphotransferases
  • Mitogen-Activated Protein Kinase 8
  • Mitogen-Activated Protein Kinases
  • Endopeptidases
  • Casp3 protein, mouse
  • Caspase 3
  • Caspases
  • Staurosporine