Study on potential antitumor mechanism of quinoline-based silver(I) complexes: Synthesis, structural characterization, cytotoxicity, cell cycle and caspase-initiated apoptosis

Three mononuclear silver(I) complexes with 8-hydroxyquinoline, 8-hydroxy-2-methylquinoline and 5-chloro-8-quinolinol were synthesized and characterized by elemental analysis, NMR, ESI-MS as well as single crystal X-ray diffraction analysis. All the structures of complexes 1–3 with the silver center adopting an approximately four-coordinated distorted tetragonal pyramid geometry were found to exhibit selective cytotoxicity against HepG2, NCI-H460, BEL-7404 and HeLa cell lines with IC50 values generally in the micromolar range (1.7–14.6 μM), but low cytotoxicity towards normal human liver cell HL-7702. A combination of flow cytometric analysis and molecular probe observation indicated that complexes 1–3 could induce HepG2 cell apoptosis. Molecular mechanism studies suggested that complexes 1–3-induced apoptosis is mediated through the intrinsic apoptotic pathway with changes in mitochondrial membrane potential by finally activating effector caspase-3/9 to trigger cell apoptosis. Further studies revealed that complexes 1 and 2 caused cell cycle arrest at S phase, while complex 3 induced G1 cell cycle arrest in HepG2 cells. Taken together, these results suggest that complexes 1–3 may be potential candidates for cancer therapy.