Pomolic acid triggers mitochondria-dependent apoptotic cell death in leukemia cell line.

Abstract

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.

• Authors: Janaina Fernandes, Ricardo Weinlich, Rachel Oliveira Castilho, Maria Auxiliadora Coelho Kaplan, Gustavo Pessini Amarante-Mendes, Cerli Rocha Gattass
• Journal: Cancer letters (Cancer Lett) Vol. 219 Issue 1 Pg. 49-55 (Feb 28 2005) ISSN: 0304-3835 [Print] Ireland
• PMID: 15694664 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acid Chloromethyl Ketones
• Cysteine Proteinase Inhibitors
• benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
• pomolic acid
• Oleanolic Acid
• CASP3 protein, human
• CASP9 protein, human
• Caspase 3
• Caspase 9
• Caspases

Topics

• Amino Acid Chloromethyl Ketones (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Caspase 3
• Caspase 9
• Caspases (drug effects, metabolism)
• Cysteine Proteinase Inhibitors (pharmacology)
• Electrophoresis, Polyacrylamide Gel
• Enzyme Activation (drug effects)
• HL-60 Cells
• Humans
• Membrane Potentials (drug effects)
• Mitochondria (drug effects)
• Oleanolic Acid (analogs & derivatives, pharmacology)