title: Corosolic acid triggers mitochondria and caspase-dependent apoptotic cell death in osteosarcoma MG-63 cells.
abstract: 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.
authors.affiliation: Department of Orthopedics, Shanghai Tenth People's Hospital, Shanghai, 200072, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Cai
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Dake
authors.initials: D
authors.lastname: Tong
authors.forename: Zhangyong
authors.initials: Z
authors.lastname: Tan
authors.forename: Dong
authors.initials: D
authors.lastname: Han
authors.forename: Fang
authors.initials: F
authors.lastname: Ji
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D012516:Osteosarcoma / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D014315:Triterpenes; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; C113861:corosolic acid; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases