Valproic acid induces apoptosis in human leukemia cells by stimulating both caspase-dependent and -independent apoptotic signaling pathways

Leuk Res. 2002 May;26(5):495-502. doi: 10.1016/s0145-2126(01)00151-5.


We investigated the effects of valproic acid (VPA) on the growth and survival of human leukemia cell lines. VPA induced cell death in all of the nine cell lines tested in a dose dependent manner. VPA-treatment induced apoptotic changes in MV411 cells including DNA fragmentation, phosphatidylserine externalization, cytochrome c release from mitochondria, and activation of caspases-3, -8, and -9. A caspase inhibitor, zVAD-FMK, inhibited the DNA fragmentation induced by VPA but not cell death. These findings suggest that VPA exerts an anti-leukemic effect by both caspase-dependent and -independent apoptotic signaling pathways.

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Apoptosis / drug effects*
  • Caspases / physiology*
  • Cytochrome c Group / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Humans
  • Leukemia / enzymology
  • Leukemia / pathology*
  • Tumor Cells, Cultured
  • Valproic Acid / pharmacology*


  • Amino Acid Chloromethyl Ketones
  • Cytochrome c Group
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • Valproic Acid
  • Caspases