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Methyl Protodioscin Induces Apoptosis in Human Osteosarcoma Cells by Caspase-Dependent and MAPK Signaling Pathways

Tseng, Shun-Cheng, Shen, Tai-Shan, Wu, Chia-Chieh, Chang, Ing-Lin, Chen, Hsin-Yao, Hsieh, Chen-Pu, Cheng, Chun-Hsiang, Chen, Chiu-Liang
Journal of agricultural and food chemistry 2017 v.65 no.13 pp. 2670-2676
Dioscorea, antagonists, antineoplastic activity, apoptosis, caspase-3, caspase-9, cell growth, cell viability, humans, membrane potential, mitochondrial membrane, mitogen-activated protein kinase, osteosarcoma, pro-apoptotic proteins, rhizomes, saponins, signal transduction
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.