Nickel(II) metallates induced intrinsic apoptotic pathway-mediated cell death in lung and breast cancer cells

New nickel(II) complexes were obtained from the reaction between 3-formylchromone-4(N)-substituted thiosemicarbazones (HL¹-HL⁴) and [NiCl₂(PPh₃)₂] in chloroform-ethanol medium. The complexes were characterised using IR, electronic, ¹H NMR ¹³C NMR, and ESI mass spectral data. The ligands (HL¹-HL⁴) coordinated to nickel ion as dibasic tridentate ONS donor by forming a five member and six member chelate rings. The binding ability of the complexes (1–4) to calf-thymus DNA and BSA has been explored by absorption and emission titration methods and based on the observations, an electrostatic binding mode and static quenching mechanism have been proposed respectively. Complexes cleaved the supercoiled DNA (pBR322 DNA) without adding any external agents. The in vitro toxicological studies of nickel(II) complexes revealed that complexes 2 and 3 have potent anticancer activity on both A549 and MDA MB 231 cell lines and are better in comparison with cisplatin. The effects of both the complexes 2 and 3 on apoptosis are related to ROS formation and loss of mitochondrial membrane potential. The over expression of caspase 9 and caspase 3, the effector and executioner caspases were shown to initiate the intrinsic apoptotic pathway, despite the down regulation of the mRNA for the essential anti-apoptotic protein BCL-2 in A549 cells. Moreover, an effective concentration of complexes 2 and 3 has been shown to activate caspase 3 and induce Poly(ADP-ribose) polymerase (PARP) cleavage in both the cell lines. Overall, the findings demonstrated that complexes 2 and 3 were effective in inducing intrinsic pathway-mediated apoptosis in cancer cell lines.