Corosolic Acid Triggers Mitochondria and Caspase‐dependent Apoptotic Cell Death in Osteosarcoma MG‐63 Cells

The response of osteosarcoma MG‐63 cells to corosolic acid treatment has been investigated. The results showed that corosolic acid significantly inhibited cell viability in both a dose and a time dependent manner. It was found that corosolic acid increased the Bax/Bcl‐2 ratio by up‐regulating Bax expression, disrupted mitochondrial membrane potential and triggered the release of cytochrome c from mitochondria into the cytoplasm. Corosolic acid treatment triggered the activation of caspase‐8, 9 and 3. The apoptosis was obviously inhibited by pretreatment with a general caspase inhibitor, z‐VAD‐FMK. Moreover, pretreatment of CsA, a cyclophilin D ligand that inhibits mitochondria potential uncoupling, prevented the activation of caspase‐9 and caspase‐3, but not caspase‐8, and the apoptosis of MG‐63 cells, triggered by corosolic acid. All these results indicated that corosolic acid‐induced apoptosis was associated with the activation of caspases via a mitochondrial pathway. Copyright © 2011 John Wiley & Sons, Ltd.