Add time:09/04/2019 Source:sciencedirect.com
Two novel ruthenium(II) polypyridyl complexes [Ru(bpy)2(ETPIP)](ClO4)2 (Ru(II)-1) and [Ru(phen)2(ETPIP)](ClO4)2 (Ru(II)-2) (bpy = 2,2′-bipyridine, ETPIP = 2-(4-(thiophen-2-ylethynyl)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline, phen = 1,10-phenanthroline) have been synthesized and characterized. The DNA binding behaviors were evaluated using electronic absorption titration, luminescence spectra and viscosity measurement, revealing an intercalative mode. The cytotoxicity of the ligand and Ru(II) complexes toward A549, HepG-2, SGC-7901 and Hela was assayed by MTT ((3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyltetrazolium bromide)) method. Notably, ETPIP shows no anticancer activity against selected cell lines, and complexes Ru(II)-1 (IC50 = 18.4 ± 2.1 μM) and Ru(II)-2 (IC50 = 16.5 ± 1.7 μM) were found to be slightly more effective against HepG-2 cells than cisplatin (IC50 = 26.4 ± 2.6 μM). Evaluation of cell invasion was performed with the Boyden chamber invasion assay. Additionally, the cell cycle distribution of HepG-2 cells was carried out by flow cytometry. Most importantly, the further anticancer mechanism of the Ru(II) complexes was explored by apoptosis, intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potentials. These results reveal that complexes Ru(II)-1 and Ru(II)-2 could induce apoptosis in HepG-2 cells via a ROS-mediated mitochondrial dysfunction pathway.
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