Study of the effect of zinc oxide, selenium, and silver nanoparticles on the expression level of oxidative stress-associated genes in ovarian cancer

Abstract

Reactive oxygen species (ROS) generated by oxidative stress have emerged as critical factors in the pathophysiology of malignancies. This study investigated the antioxidant and anticancer properties of zinc (Zn), selenium (Se), and silver (Ag) nanoparticles (NPs) against the A2780 human ovarian cancer cell line. Here, the bioinformatics approach was used to determine the top differentially expressed genes associated with oxidative stress. The ZnO-, Se-, and Ag-NPs were then synthesized via a green synthesis method and subsequently characterized using techniques, such as FTIR, XRD, DLS, zeta potential analysis, FESEM, and TEM. The antioxidant capacity of the NPs was evaluated using a DPPH scavenging assay and their effect on superoxide dismutase enzyme activity was determined. HDF and A2780 cells were treated with varying concentrations of ZnO-, Se-, and Ag-NPs, and cell viability and colony formation were assessed using MTT and clonogenic assays, respectively. Additionally, qPCR was performed to analyze the expression of the candidate genes NOX4, SOD2, and NR4A4. Characterization techniques confirmed the successful synthesis of pure, crystalline, and spherical NPs. Antioxidant assays demonstrated the significant antioxidant properties of ZnO-, Se-, and Ag-NPs. In vitro studies indicated that ZnO-, Se-, and Ag-NPs effectively inhibited cell proliferation and suppressed colony formation, likely owing to the downregulation of NOX4 and upregulation of SOD2 genes. Our findings suggest that ZnO-, Se-, and Ag-NPs may serve as promising anticancer agents for ovarian cancer and NOX4 downregulation and SOD2 upregulation can be proposed as oxidative stress biomarkers; however, further experimental investigation is required to elucidate the therapeutic potential of NPs and the early detection potential of biomarkers.

Keywords: Ovarian cancer; Selenium nanoparticle; Silver nanoparticle; Stress-oxidative pathway; Zinc nanoparticle.