Anticancer approach of zinc oxide nanocomposite prepared by gamma radiation via induction of apoptosis and PGC‐1α pathways in hepatocellular carcinoma in rats

Abstract

Zinc oxide nanoparticles (ZnO NPs) are attracting the interest of researchers due to their potential applications in cancer treatment. It was recently shown that ZnO NPs specifically destroy cancer cells. However, the underlying molecular processes that drive ZnO NPs' anticancer activity are unclear. Radical polymerization was used for synthesizing zinc oxide nanoparticles using gamma radiation. Polyvinylpyrrolidone (PVP) was employed as a stabilizer in the production of zinc oxide nanoparticles using zinc nitrate. PVP@ZnO nanostructures were characterized using a number of techniques, including high‐resolution transmission electron microscopy (HRTEM) and UV–visible spectroscopy. Fourier‐transform infrared spectroscopy (FTIR) was used to study the functional groups of the produced nanostructures. Moreover, the surface morphology of prepared zinc oxide nanoparticles (ZnO NPs) and PVP@ZnO nanostructures was shown using SEM. In addition, the crystalline structure of the aforementioned samples was identified and investigated via XRD. The current work examined the anticancer effect of ZnO nanocomposite against rat hepatocellular carcinoma (HCC). The results demonstrated that ZnO nanocomposite exert distinct effects on apoptosis and PGC‐1α pathways in hepatocellular carcinoma in rats. mRNA levels of tumor suppressor gene p53 and antiapoptotic gene BCL‐2 were downregulated, while the apoptotic gene Bax was upregulated and Caspase‐3 activity increased in diethylnitrosamine (DEN) + ZnO nanocomposite‐treated rats in comparison with DEN‐treated rats. ZnO nanocomposite were also found to have an effect on liver function (ALT, AST, ALP, and GGT) and total antioxidant capacity (TAC). Treatment with DEN manifested a significant decrease in the expression of mtTFA and PGC‐1α (mtTFA: 0.54 fold and PGC‐1α: 0.31 fold in respect to the normal control), while ZnO nanocomposite treatment induced a remarkable increase in their expression. In conclusion, the present data demonstrated that ZnO nanocomposite showed anticancer activity via induction of apoptosis and PGC‐1α pathways. In addition, improvements in liver function and antioxidant capacity.