Journal
LEUKEMIA RESEARCH
Volume 26, Issue 5, Pages 495-502Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0145-2126(01)00151-5
Keywords
valproic acid; apoptosis; leukemia; caspase-dependent and -independent pathways
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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. (C) 2002 Elsevier Science Ltd. All rights reserved.
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