Eldecalcitol induces apoptosis and autophagy in human osteosarcoma MG-63 cells by accumulating ROS to suppress the PI3K/Akt/mTOR signaling pathway

• Published in: Cellular signalling 2021-02, Vol.78, p.109841-109841, Article 109841
• Main Authors: Zhang, Chaotao, Huang, Cancan, Yang, Panpan, Li, Congshan, Li, Minqi
• Format: Article
• Language: English
• Subjects: Apoptosis; Autophagy; Eldecalcitol; Osteosarcoma; PI3K/Akt/mTOR pathway; ROS
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2020.109841

Eldecalcitol (ED-71) is a new type of vitamin D analog, and vitamin D has been reported to have therapeutic effects in infectious disease, autoimmune disease, and cancer. However, the anti-cancer effect of ED-71 remains unclear. The objective of this study was to explore the anti-cancer effect of ED-71 in human osteosarcoma cells and to identify the related mechanism. The CCK8 assay results showed that ED-71 inhibited MG-63 cell viability in dose and time dependent manners. Cloning and Transwell invasion assays showed that ED-71 inhibited clonal and invasion ability of MG-63 cells. Flow cytometry results showed ED-71 the G2/M cycle arrest rate, apoptosis, and intracellular ROS. Western blot was used to detect cleaved-caspase-3, Bax, Bcl-2, LC3-II/LC3-I, and P62 levels and the mTOR pathway. The increase of LC3-II and P62 indicated that ED-71 induced the formation of autophagosomes and inhibited autophagy flux. Furthermore, ED-71-induced apoptosis was weakened after adding 3-methyladenine and ED-71-induced early autophagy was weakened by caspase-3 inhibitor (Z-VAD-FMK), which indicated the two processes active each other in the presence of ED-71. Furthermore, N-acetylcysteine (NAC) pretreatment reversed the ED-71-treatment outcomes, including increased apoptosis and autophagy and inhibition of the PI3K/Akt/mTOR pathway. In conclusion, our results reveal that ED-71 induced G2/M arrest, apoptosis and autophagy in MG-63 cells by accumulating ROS to suppress the PI3K/Akt/mTOR signaling pathway •ED-71 induced early autophagy and apoptosis in MG-63 cells.•Autophagy induced by ED-71 lead to cell death rather than survival by inducing apoptosis.•Autophagy and apoptosis induced by ED-71 promoted each other.•Autophagy and apoptosis induced by ED-71 were regulated by accumulating ROS to suppress the PI3K/Akt/mTOR signaling pathway.