Biosynthesized gold nanoparticles using leaf extract of Citrus medica inhibit hepatocellular carcinoma through regulation of the Wnt/β-catenin signaling pathway

Abstract

Gold nanoparticle (AuNPs) influence the biomedical sciences owing to different potential characteristics and potential features. To date, the bioinspired fabrication of AuNPs is further recognized due to their safety and efficacy. In this study, we synthesized AuNPs using leaf extract of Citrus medica (C. medica) and well-characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and UV–visible analyses. Afterward the selective anticancer effects of biosynthesized AuNPs against HepG2 cells were evaluated by different techniques including MTT, oxidative markers, qPCR, and western blot assays.The results showed that the polyphenols of the C. medica leaf extract was responsible for the bioinspired reduction and stability of the AuNPs with a powder size in the range of 20–50 nm. Additionally, it was seen that biosynthesized AuNPs show selective inhibition on the proliferation of HepG2 (human liver cancer cell line) relative to THLE3 (normal adult liver epithelial cells) via generation of ROS and MDA, reduction of GSH level and SOD activity, and over expression of Bax/Bcl-2 and Caspase-3 mRNA. It was also shown that biosynthesized AuNPs regulate the Wnt signaling pathway through upregulation of phosphorylated GSK-3β known as the inactivated form of GSK-3β and downregulation of β-catenin and Cyclin-D1 at protein level. This study may hold great promise for development of NP-based anticancer agents, although it needs further investigations in vivo.