Molecular Mechanism of Cytotoxicity, Genotoxicity, and Anticancer Potential of Green Gold Nanoparticles on Human Liver Normal and Cancerous Cells

Abstract

Nanomaterials are extensively applied in various fields such as industry, medicine, and food and drugs due to their unique properties. In this study, gold nanoparticles were biosynthesized using leaf extract of Azadirachta indica and chloroauric acid salt. We have determined the cytotoxicity, genotoxicity, and apoptotic effect of green gold nanoparticles (gGNPs) on human normal (CHANG) and liver cancer (HuH-7) cells. Before exposure to cells, physiochemical characteristic of gGNPs was characterized using a transmission electron microscope and dynamic light scattering. Cytotoxicity of gGNPs was found dose-dependent, as it was confirmed using 2 methods, namely, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide and neutral red uptake. The gGNPs provoked intracellular reactive oxygen species (ROS), lipid peroxide, and reduced total glutathione and mitochondrial membrane potential in CHANG and HuH-7 cells in a dose-dependent manner. We have observed that N-acetyl-l-cysteine inhibits the generation of ROS in both cells after exposure to gGNPs. DNA damaging effects of gGNPs were determined by comet assay, and the maximum DNA damage was observed at 700 µg/mL gGNPs for 24 hours. It was observed that HuH-7 cells are slightly more sensitive to gGNPs exposure than CHANG cells. In conclusion, cytotoxicity and apoptosis in CHANG and HuH-7 cells due to gGNPs were mediated through oxidative stress.