Pomolic acid triggers mitochondria-dependent apoptotic cell death in leukemia cell line.
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.
Fernandes
Janaina
J
Instituto de Biofísica Carlos Chagas Filho, UFRJ, Ilha do Fundao, IBCCF, CCS Bl.G, Rio de Janeiro 21949-900, Brazil.
Weinlich
Ricardo
R
Castilho
Rachel Oliveira
RO
Kaplan
Maria Auxiliadora Coelho
MA
Amarante-Mendes
Gustavo Pessini
GP
Gattass
Cerli Rocha
CR
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000590:Amino Acid Chloromethyl Ketones; D015853:Cysteine Proteinase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C115535:pomolic acid; D009828:Oleanolic Acid; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases