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

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

  • Cell Signal. 2021 Feb;78:109841. doi: 10.1016/j.cellsig.2020.109841.
Chaotao Zhang 1,  Cancan Huang 1,  Panpan Yang 1,  Congshan Li 1,  Minqi Li 2
Affiliations

Affiliations

  • 1 Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Shandong Key Laboratory of Oral Tissue Regeneration, Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan 250012, China.
  • 2 Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Shandong Key Laboratory of Oral Tissue Regeneration, Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan 250012, China. Electronic address: [email protected].
PMID: 33217539 DOI: 10.1016/j.cellsig.2020.109841
Abstract

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.

Keywords

Apoptosis; Autophagy; Eldecalcitol; Osteosarcoma; PI3K/Akt/mTOR pathway; ROS.

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