title: Ursolic Acid Triggers Apoptosis in Human Osteosarcoma Cells via Caspase Activation and the ERK1/2 MAPK Pathway.
abstract: Ursolic acid (UA), a naturally occurring pentacyclic triterpene acid found in many medicinal herbs and edible plants, has been shown to trigger apoptosis in several lines of tumor cells in vitro. We found that treatment with UA suppressed the viability of human osteosarcoma MG-63 cells and induced cell cycle arrest at sub-G1 and G2/M phases. Furthermore, exposure to UA induced intracellular oxidative stress and collapse of mitochondrial membrane permeability, resulting in the subsequent activation of apoptotic caspases 8, 9, and 3 as well as PARP cleavage, and ultimately apoptosis in MG-63 cells. Moreover, protein analysis of mitogen-activated protein kinase (MAPK)-related protein expression showed an increase in activated ERK1/2, JNK, and p38 MAPK in UA-treated MG-63 cells. In addition, UA-induced apoptosis was significantly abolished in MG-63 cells that had been pretreated with inhibitors of caspase 3, 8, and 9 and ERK1/2. Furthermore, UA-treated MG-63 cells also exhibited an enhancement in Bax/Bcl-2 ratio, whereas anti-apoptotic XIAP and survivin were down-regulated. Taken together, we provide evidence demonstrating that UA mediates caspase-dependent and ERK1/2 MAPK-associated apoptosis in osteosarcoma MG-63 cells.
authors.affiliation: Orthopedics & Sports Medicine Laboratory, Changhua Christian Hospital , Changhua 50006, Taiwan.|Department of Orthopedic Surgery, Changhua Christian Hospital , Changhua 50006, Taiwan.|Institute of Biomedical Sciences, National Chung Hsing University , Taichung 40227, Taiwan.
authors.forename: Chia-Chieh
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Orthopedics & Sports Medicine Laboratory, Changhua Christian Hospital , Changhua 50006, Taiwan.
authors.forename: Chun-Hsiang
authors.initials: CH
authors.lastname: Cheng
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University , Taichung 40227, Taiwan.
authors.forename: Yi-Hui
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Orthopedic Surgery, Changhua Christian Hospital , Changhua 50006, Taiwan.
authors.forename: Ing-Lin
authors.initials: IL
authors.lastname: Chang
authors.affiliation: Department of Orthopedic Surgery, Changhua Christian Hospital , Changhua 50006, Taiwan.
authors.forename: Hsin-Yao
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Orthopedics & Sports Medicine Laboratory, Changhua Christian Hospital , Changhua 50006, Taiwan.|Department of Orthopedic Surgery, Changhua Christian Hospital , Changhua 50006, Taiwan.
authors.forename: Chen-Pu
authors.initials: CP
authors.lastname: Hsieh
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University , Taichung 40227, Taiwan.|Department of Biotechnology, Asia University , Taichung 41354, Taiwan.|Graduate Institute of Basic Medicine, China Medical University , Taichung 40402, Taiwan.|Department of Medical Research, China Medical University Hospital , Taichung 40402, Taiwan.
authors.forename: Pin-Ju
authors.initials: PJ
authors.lastname: Chueh
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001859:Bone Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism*; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D012516:Osteosarcoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020928:Mitogen-Activated Protein Kinases; D014315:Triterpenes; D000097245:Ursolic Acid
keywords: MAPK; MG-63 cells; apoptosis; caspase; ursolic acid