zVAD-fmk and DEVD-cho induced late mitosis arrest and apoptotic expressions.
Cell growth in human Chang liver cells was arrested in late mitosis with 600 microM zVAD-fmk. Associated cell death manifested cell shrinkage and phagocytic marking shown by phosphatidylserine (PS) externalization, in a dose-dependent manner. While low molecular weight internucleosomal ladder cleavages were suppressed, there were however high molecular weight DNA cleavages extending up to megabase level in association with chromatin condensation that appeared more marked than the staurosporine-induced positive-apoptosis control. Caspase-3 activity was suppressed. Specific caspase-3 inhibitor DEVD-cho also produced cell growth suppression with late mitosis arrest, and cell shrinkage which was expressed concomitantly with phagocytic PS marking in similar dose-dependent manners at 50 to 100 microM concentrations. Cell shrinkage, PS externalization, and high molecular weight DNA cleavages associated with chromatin condensation without 200 bp ladder fragmentations, were dissociated from caspase-3 activity. Anti-caspases inducing late mitosis arrest provided fresh insights into late mitosis progression.
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Department of Anatomy, Faculty of Medicine, National University of Singapore, Kent Ridge.
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D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002452:Cell Count; D002478:Cells, Cultured; D053938:DNA Fragmentation; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000378:metabolism
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D009842:Oligopeptides; D010718:Phosphatidylserines; C108637:aspartyl-glutamyl-valyl-aspartal; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases