Apoptosis induction by Co-MGC and Ni-MGC against pancreatic cancer cells and their interaction with DNA

Abstract

Pancreatic carcinoma ranks among the most aggressive malignancies. Although chemotherapeutic agents constitute the cornerstone of treatment regimens, drug resistance and dose-limiting toxicities significantly compromise therapeutic efficacy, necessitating innovative antitumor agents. In this study, two transition metal complexes, Co-MGC and Ni-MGC, were synthesized using 4-((4-(pyridin-3-yl)pyrimidin-2-ylamino)methyl)benzoic acid (MGC) as the ligand via solvothermal synthesis. Molecular docking simulations revealed their capacity to bind DNA base pairs through hydrogen bonding and intercalate into the duplex, thereby disrupting DNA structural integrity. Subsequently, the mechanism was verified by FS-DNA using agarose gel electrophoresis, UV-Vis spectroscopy, and fluorescence spectroscopy. FITC labeling confirmed cellular uptake, while DCFH-DA and JC-1 probes demonstrated intracellular ROS generation and reduction in the high mitochondrial membrane potential (ΔΨ_m) cell population to 65.53% (Co-MGC) and 71.9% (Ni-MGC), respectively. Cytotoxicity analysis revealed that Co-MGC and Ni-MGC exhibited half-maximal inhibitory concentrations (IC₅₀) of 8.28 µM and 10.23 µM, respectively, against BxPC-3 cells. Both of the complexes induced apoptosis over 35% at lower dose.