title: Valproic acid induces apoptosis in human leukemia cells by stimulating both caspase-dependent and -independent apoptotic signaling pathways.
abstract: 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.
authors.affiliation: Department of Pediatrics, Kobe University School of Medicine, Hyogo, Japan.
authors.forename: Rika
authors.initials: R
authors.lastname: Kawagoe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawagoe
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Sano
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000502:physiology*; D003574:Cytochrome c Group / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006801:Humans; D007938:Leukemia / Q000201:enzymology / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D003574:Cytochrome c Group; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D014635:Valproic Acid; D020169:Caspases