Cantharidin Inhibits Anti-Apoptotic Bcl-2 Family Proteins and Induces Apoptosis in Human Osteosarcoma Cell Lines MG-63 and MNNG/HOS via Mitochondria-Dependent Pathway
Shoumin Feng, Jian Zhu, Kaishun Xia, Wei Yu, Yitian Wang, Junjie Wang, Fangcai Li, Zhengming Yang, Xiaobo Yang, Bing Liu, Huimin Tao, Chengzhen Liang
(Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland))
Med Sci Monit 2018; 24:6742-6749
Cantharidin (CTD) is one of the major active ingredients of blister beetles and has significant antitumor activity in many cancer cell lines. The aim of our study was to evaluate the effect of CTD on the apoptosis of human osteosarcoma cells MG-63 and MNNG/HOS, and to explore the possible molecular mechanism.
MATERIAL AND METHODS: Osteosarcoma cells MG-63 and MNNG/HOS were treated with varying concentrations of CTD. The proliferation inhibition of cells was detected by MTS. Flow cytometry and Hoechst 33258 staining were used to determine cell cycle arrest and apoptosis, and apoptosis-related protein levels were analyzed by Western blotting.
RESULTS: Our current findings suggest that CTD could inhibit the proliferation of these 2 osteosarcoma cells. The cells treated with CTD showed an obvious apoptotic morphology, and CTD promoted cells apoptosis in a dose-dependent manner. In addition, cantharidin-induced apoptosis was accompanied by increased expression of Bax and PARP and decreased expression of Bcl-2, p-Akt, and p-Cdc2.
CONCLUSIONS: CTD accelerates the apoptosis of MG-63 and MNNG/HOS cells in a concentration-dependent manner through the mitochondria-dependent pathway, suggesting that use of CTD is a novel approach for the treatment of osteosarcoma.
Keywords: Apoptosis, Cantharidin, Mitochondria, Osteosarcoma