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

Drug Dev Res. 2024 Nov;85(7):e22265. doi: 10.1002/ddr.22265.

Abstract

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.

Keywords: 8‐hydroxyquinoline derivatives; antitumor activity; apoptosis; lanthanide complex.

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Apoptosis* / drug effects
  • Cell Cycle / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology
  • Drug Screening Assays, Antitumor
  • Humans
  • Lanthanoid Series Elements / chemistry
  • Lanthanoid Series Elements / pharmacology
  • Membrane Potential, Mitochondrial / drug effects
  • Oxyquinoline* / chemistry
  • Oxyquinoline* / pharmacology
  • Reactive Oxygen Species / metabolism

Substances

  • Antineoplastic Agents
  • Oxyquinoline
  • Coordination Complexes
  • Lanthanoid Series Elements
  • Reactive Oxygen Species