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 60 0 mu M zVAD-fmk. Associated cell death manifested cell shrinkage and phagoc ytic marking shown by phosphatidylserine (PS) externalization, in a dose-de pendent manner. While low molecular weight internucleosomal ladder cleavage s were suppressed, there were however high molecular weight DNA cleavages e xtending up to megabase level in association with chromatin condensation th at appeared more marked than the staurosporine-induced positive-apoptosis c ontrol. Caspase-3 activity was suppressed. Specific caspase-3 inhibitor DEV D-cho also produced cell growth suppression with late mitosis arrest, and c ell shrinkage which was expressed concomitantly with phagocytic PS marking in similar dose-dependent manners at 50 to 100 mu M concentrations. Cell sh rinkage, PS externalization, and high molecular weight DNA cleavages associ ated with chromatin condensation without 200 bp ladder fragmentations, were dissociated from caspase-3 activity. Anticaspases inducing late mitosis ar rest provided fresh insights into late mitosis progression.