Role of Green-Synthesized Silver and Copper Oxide Nanoparticles in Modulating DNA Topoisomerase III Activity and DNA Methyltransferase I Protein Expression Through In Vitro and In Silico Approaches
摘要
Silver nanoparticles (Ag NPs) of various shapes and sizes, along with anisotropic copper oxide (CuO) NPs, including nanocubes, nanorods, and nanospikes, were synthesized using a green approach with plant extracts from three different polyherbal formulations. Both Ag and CuO nanoparticles were tested for their antibacterial effects on Staphylococcus aureus and Escherichia coli, and results showed that CuO nanoparticles had stronger antibacterial activity against both bacterial strains compared to AgNPs. Additionally, the cytotoxic effects of both Ag and CuO NPs on pancreatic cancer cells (MIA PaCa-2) were evaluated using the MTT viability assay. AgNPs showed the strongest cytotoxicity, eliminating 80–85% of cancer cells at significantly lower doses (2.5 and 5 µg/mL) than the anisotropic CuO NPs produced using the same polyherbal extracts. DNA relaxation studies showed that quasi-spherical AgNPs exhibited greater inhibitory activity against DNA topoisomerase III alpha than anisotropic CuO NPs. Additionally, our analysis of protein expression using western blot showed that Ag NPs specifically target the proteins DNA methyltransferase DNMT1 and DNA topoisomerase III alpha (TOP3A). Furthermore, density functional theory (DFT) analysis was employed to investigate the interactions at the atomic and electronic levels of the plant extract compounds, predicting HOMO and LUMO energies and molecular electrostatic potentials, which provide insight into their electronic properties, reactivity, and stability.