title: Methyl Protodioscin Induces Apoptosis in Human Osteosarcoma Cells by Caspase-Dependent and MAPK Signaling Pathways.
abstract: Methyl protodioscin (MPD), a furostanol saponin derived from the rhizomes of Dioscorea collettii var. hypoglauca (Dioscoreaceae), has been shown to exhibit broad bioactivities such as anti-inflammation and antitumor activities. Here, we explored the molecular mechanisms by which MPD induced apoptosis in MG-63 cells. The data showed that MPD significantly suppressed cell growth (cell viabilities: 22.5 ± 1.9% for 8 μM MPD versus 100 ± 1.4% for control, P < 0.01) and enhanced cell apoptosis. The exposure to MPD resulted in a significant induction of reactive oxygen species, loss of mitochondrial membrane potential, and activation of caspase-9 and caspase-3 (P < 0.01, all cases). Furthermore, treatment with MPD increased the levels of phosphorylated JNK and p38 MAPK and markedly decreased the levels of phosphorylated ERK in MG-63 cells. Co-administration of the JNK-specific antagonist, the p38-specific antagonist, or the caspase antagonist (P < 0.05, all cases) has reversed the apoptotic effects in MPD treatment. We also found that exposure to MPD resulted in a significant reduction in the protein level of anti-apoptotic proteins Bcl-2, survivin, and XIAP (P < 0.05, all cases). In conclusion, our results indicate that MPD induces apoptosis of human osteosarcoma MG-63 cells, at least in part, by caspase-dependent and MAPK signaling pathways.
authors.affiliation: Department of Orthopedic Surgery, Changhua Christian Hospital , Changhua 50006, Taiwan, R.O.C.
authors.forename: Shun-Cheng
authors.initials: SC
authors.lastname: Tseng
authors.affiliation: Department of Orthopedic Surgery, Changhua Christian Hospital , Changhua 50006, Taiwan, R.O.C.
authors.forename: Tai-Shan
authors.initials: TS
authors.lastname: Shen
authors.affiliation: Department of Orthopedic Surgery, Changhua Christian Hospital , Changhua 50006, Taiwan, R.O.C.|Orthopedics & Sports Medicine Laboratory, Changhua Christian Hospital , Changhua 50006, Taiwan, R.O.C.|Institute of Biomedical Sciences, National Chung Hsing University , Taichung 40227, Taiwan, R.O.C.|School of Medicine, Kaohsiung Medical University , Kaohsiung 80708, Taiwan, R.O.C.
authors.forename: Chia-Chieh
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Department of Orthopedic Surgery, Changhua Christian Hospital , Changhua 50006, Taiwan, R.O.C.
authors.forename: Ing-Lin
authors.initials: IL
authors.lastname: Chang
authors.affiliation: Department of Orthopedic Surgery, Changhua Christian Hospital , Changhua 50006, Taiwan, R.O.C.
authors.forename: Hsin-Yao
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Department of Orthopedic Surgery, Changhua Christian Hospital , Changhua 50006, Taiwan, R.O.C.|Orthopedics & Sports Medicine Laboratory, Changhua Christian Hospital , Changhua 50006, Taiwan, R.O.C.
authors.forename: Chen-Pu
authors.initials: CP
authors.lastname: Hsieh
authors.affiliation: Orthopedics & Sports Medicine Laboratory, Changhua Christian Hospital , Changhua 50006, Taiwan, R.O.C.
authors.forename: Chun-Hsiang
authors.identifier: http://orcid.org/0000-0003-1580-7184
authors.initials: CH
authors.lastname: Cheng
authors.affiliation: Department of Orthopedic Surgery, Changhua Christian Hospital , Changhua 50006, Taiwan, R.O.C.|Department of Nursing, Da Yeh University , Changhua 51591, Taiwan, R.O.C.
authors.forename: Chiu-Liang
authors.initials: CL
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D027742:Dioscorea / Q000737:chemistry*; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D012516:Osteosarcoma / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D012503:Saponins / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D010936:Plant Extracts; D012503:Saponins; D051028:bcl-2-Associated X Protein; C425324:methyl protodioscin; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053453:Caspase 9; D004144:Diosgenin
keywords: MAPK pathways; MG-63 cells; apoptosis; caspase; methyl protodioscin