benzyloxycarbonylvalyl-alanyl-aspartyl-fluoromethyl-ketone and pomolic-acid

One of the major goals in chemotherapy is to circumvent anti-apoptotic strategies developed by tumor cells. In a previous paper, we showed that pomolic acid (PA) is able to kill the leukemia cell line K562 and its MDR derivative, Lucena 1. Here, we demonstrated that PA-induced apoptosis of HL-60 cells is dependent on the activation of caspases-3 and -9 and dissipation of the mitochondrial transmembrane potential (Deltapsim). Disruption of Deltapsim precedes caspase activation and is not inhibited by zVAD-fmk indicating mitochondria as the main target of PA. Our data pointed to the potential use of PA to overcome apoptosis resistance.

Topics: Amino Acid Chloromethyl Ketones; Apoptosis; Blotting, Western; Caspase 3; Caspase 9; Caspases; Cysteine Proteinase Inhibitors; Electrophoresis, Polyacrylamide Gel; Enzyme Activation; HL-60 Cells; Humans; Membrane Potentials; Mitochondria; Oleanolic Acid