Green synthesized zinc oxide nanoparticles induce apoptosis by suppressing PI3K/Akt/mTOR signaling pathway in osteosarcoma MG63 cells

Abstract

This study aimed to assess the apoptosis-inducing mechanism of zinc oxide nanoparticles (ZnO NPs) stabilized by Solanum xanthocarpum plant extract in human osteosarcoma MG63 cells. In the present study, we synthesized ZnO NPs from S. xanthocarpum extract and evaluated its anticancer mechanism on MG 63 cells. The synthesized ZnO NPs were characterized by ultraviolet spectroscopy, X-ray crystallography, transmission electron microscopy, energy dispersive X-ray, and Fourier-transform infrared spectroscopy analysis. The mean size of the synthesized ZnO NPs was 21.62 ± 7.45 nm and spherical in shape. The cytotoxicity of ZnO NPs on MG63 cells was determined by MTT assay. The Western blot analysis was carried out to examine the expression of apoptotic and autophagy-related proteins in MG63 cells. The findings of the study reveal that ZnO NPs treatment showed concentration-dependent cytotoxicity, increased lipid peroxidation, decreased antioxidant activity, increased reactive oxygen species generation, and increased DNA damage. In addition, ZnO NPs treatment increased the expression of apoptotic members such as p53, Bax, caspase-3, -8, and -9 while downregulating Bcl-2 expression in MG63 cells. Furthermore, ZnO NPs treatment suppressed the P13K/AKT/mTOR signaling pathway and increased the expression of LC3 and beclin-1 in MG63 cells. The present study demonstrated that ZnO NPs induced apoptosis and autophagy in MG63 cells through modifying apoptotic and autophagy-related proteins.