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

Abstract Four lanthanide complexes with 8‐hydroxyquinoline‐2‐aldehyde‐2‐hydrazinopyridine (H‐L 1 ), 8‐hydroxyquinoline‐2‐aldehyde‐2‐hydrazimidazole (H‐L 2 ): [Sm(L 1 ) 2 ][Sm(L 1 )(NO 3 ) 3 ] · CHCl 3 · 2CH 3 OH ( 1 ), [Gd(L 1 ) 2 ][Gd(L 1 )(NO 3 ) 3 ] · CHCl 3 · 2CH 3 OH ( 2 ), [Sm(L 2 )(NO 3 ) 2 ] 2 · CH 3 OH ( 3 ), and [Eu(L 2 )(NO 3 ) 2 ] 2 · CH 3 OH ( 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 Ca 2+ 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.