Echinocystic acid induces apoptosis in HL-60 cells through mitochondria-mediated death pathway.

Echinocystic acid (EA) is a natural triterpone enriched in various herbs and used for medicinal purpose in many Asian countries. In the present study, we reported that EA can induce apoptosis in human promyelocytic leukemia cells (HL-60), as characterized by DNA fragmentation, poly (ADP) ribose polymerase cleavage. The efficacious induction of apoptosis was observed at 100 microM for 6 h. Further molecular analysis showed that EA induced the cleavage of Bid protein, the loss of mitochondrial membrane potential (DeltaPsim) cytochrome c release from mitochondria into cytosol, and activation of caspase-3, -8 and -9. However, EA did not generate reactive oxygen species (ROS), and antioxidants including N-acetyl cysteine and catalase could not block EA-induced apoptosis in the HL-60 cells. These data suggest that EA induces apoptosis in HL-60 cells through ROS-independent mitochondrial dysfunction pathway.