pepstatin and Leukemia

In this study, we investigated the effects of synthetic 6'-benzyloxy-4-bromo-2'-hydroxychalcone on viabilities of seven human leukaemia cells. It was cytotoxic against U-937, HL-60, K-562, NALM-6, MOLT-3 cells, and also against Bcl-2-overexpressing U-937/Bcl-2 cells and P-glycoprotein-overexpressing K-562/ADR, but had no significant cytotoxic effects against quiescent or proliferating human peripheral blood mononuclear cells. This chalcone is a potent apoptotic inducer in human leukaemia U-937 cells. Cell death was (i) mediated by the activation and the cleavage of initiator and executioner caspases and poly(ADP-ribose) polymerase; (ii) prevented by the pan-caspase inhibitor z-VAD-fmk, and by the selective caspase-3/7, -6 and -8 inhibitors, and by a cathepsins B/L inhibitor; (iii) associated with the release of mitochondrial proteins, including cytochrome c and Smac/DIABLO; (iv) accompanied by dissipation of the mitochondrial membrane potential, (v) partially blocked by the inhibition of p38

Topics: Antineoplastic Agents; Apoptosis; Caspase 8; Cathepsin D; Cell Line, Tumor; Cell Survival; Chalcone; Humans; Leukemia; Membrane Potential, Mitochondrial; Pepstatins; Reactive Oxygen Species