Cobalt oxide nanoparticles functionalized with glucose and conjugated to Ellagic acid (Co3O4@Glu-Ellagic acid NPs) induce apoptotic genes in HepG2, liver cancer cell line

Abstract

Surface modification of metal nanoparticles can be a solution to obtain more efficient and biocompatible drugs. In this study, the anticancer mechanism of cobalt oxide nanoparticles (NPs) functionalized with glucose and conjugated with Ellagic acid (Co3O4@Glu-Ellagic acid NPs) in a liver cancer cell line was investigated. Physicochemical characteristics of NPs were investigated by Fourier-transform infrared spectroscopy (FT-IR), Transmission electron microscopy (TEM), (Scanning Electron Microscopy) SEM, X-Ray diffraction analysis (XRD), Energy Dispersive Spectroscopy mapping (EDS-mapping), Dynamic light scattering (DLS), and zeta potential. Cytotoxicity of Co3O4@Glu-Ellagic acid NPs in normal (THLE2) and cancer (HepG2) hepatocyte cell lines was characterized by MTT and flow cytometry assays. Relative expression of the CASP8, CASP9, and p53 genes was assessed by Real-Time PCR. The synthesized nanoparticles were spherical, without considerable agglomeration, and their size was in the range of 20 to 60 nm. Surface charge and DLS size were − 30.1 mV and 280 nm, respectively. Treatment of the studied cells with the nanoparticles displayed their antiproliferative potential; however, liver cancer cells were considerably more sensitive to the nanoparticles than normal hepatocyte cells. The 50 % inhibitory concentration of Co3O4@Glu-Ellagic acid NPs for normal and cancer hepatocyte cells were 201 and 97 μg/mL, respectively. Treating HepG2 cells with Co3O4@Glu-Ellagic acid NPs led to a significant increase in the percentage of apoptotic cells (from 0.66 % to 50.8 %) and expression of the CASP8, CASP9, and p53 genes by 2.88, 2.11, and 2.0 folds that suggests apoptogenic property of the nanoparticles through activation of the intrinsic and extrinsic apoptosis pathways. Measuring Reactive Oxygen Species (ROS) level showed that in treated cancer cells with Co3O4@Glu-Ellagic acid nanoparticles the ROS level increased. Moreover, Hoechst staining indicated the anti-tumor effect of Co3O4@Glu-Ellagic acid NP by appearance of apoptotic bodies in HepG2 cells. This work revealed that Co3O4@Glu-Ellagic acid NPs are potent apoptogenic agent against liver cancer cells.