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.