Sm(Ⅲ), Gd(Ⅲ), and Eu(Ⅲ) complexes with 8‐hydroxyquinoline derivatives as potential anticancer agents via inhibiting cell proliferation, blocking cell cycle, and inducing apoptosis in NCI‐H460 cells

Four lanthanide complexes with 8-hydroxyquinoline-2-aldehyde-2-hydrazinopyridine (H-L¹), 8-hydroxyquinoline-2-aldehyde-2-hydrazimidazole (H-L²): [Sm(L¹)₂][Sm(L¹)(NO₃)₃]·CHCl₃·2CH₃OH (1), [Gd(L¹)₂][Gd(L¹)(NO₃)₃]·CHCl₃·2CH₃OH (2), [Sm(L²)(NO₃)₂]₂·CH₃OH (3), and [Eu(L²)(NO₃)₂]₂·CH₃OH (4) were synthesized and characterized. In vitro cytotoxicity evaluation showed that the ligands and four lanthanide complexes exhibited cytotoxicity to the five tested tumor cell lines. Among them, complex 1 showed the best antiproliferative activity against NCI-H460 tumor cells. Mechanistic studies demonstrated that complex 1 arrested the cell cycle of NCI-H460 cells in G1 phase and induced mitochondria-mediated apoptosis, which resulted in the loss of mitochondrial membrane potential, enhanced intracellular Ca²⁺ levels and reactive oxygen species generation. In addition, complex 1 affected the expression levels of intracellular apoptosis-related proteins and activated the caspase-3/9 in NCI-H460 cells. Therefore, complex 1 is a potential anticancer agent.