The induction of apoptosis in HepG-2 cells by ruthenium(II) complexes through an intrinsic ROS-mediated mitochondrial dysfunction pathway

Four new ruthenium(II) polypyridyl complexes [Ru(N-N)(2)(dhbn)](ClO4)(2) (N-N = dmb: 4,4'-dimethyl-2,2'-bipyridine 1; bpy = 2,2'-bipyridine 2; phen = 1,10-phenanthroline 3; dmp = 2,9-dimethyl-1,10-phenanthroline 4) were synthesized and characterized. The cytotoxicity in vitro of the ligand and complexes toward HepG-2, HeLa, MG-63 and A549 were assayed by MIT method. The IC50 values of the complexes against the above cells range from 17.7 +/- 1.1 to 45.1 +/- 2.8 mu M. The cytotoxic activity of the complexes against HepG-2 cells follows the order of 4 > 2 > 3 > 1. Ligand shows no cytotoxic activity against the selected cell lines. Cellular uptake, apoptosis, comet assay, reactive oxygen species, mitochondrial membrane potential, cell cycle arrest, and the expression of proteins involved in apoptosis pathway induced by the complexes were investigated. The results indicate that complexes 1-4 induce apoptosis in HepG-2 cells through an intrinsic ROS-mediated mitochondrial dysfunction pathway. (C) 2016 Elsevier Masson SAS. All rights reserved.