Protein binding and anticancer activity studies of ruthenium(II) polypyridyl complexes toward BEL-7402 cells

Abstract Four new ruthenium(II) polypyridyl complexes [Ru(dmb) 2 (dqtbt)](ClO 4 ) 2 ( 1 ) (dqtbt = 12-(2,3-diphenyl-quinoxalin-6-yl)-4,5,10,13-tetraazabenzo[ b ]triphenylene, dmb = 4,4′-dimethyl-2,2′-bipyridine), [Ru(bpy) 2 (dqtbt)](ClO 4 ) 2 ( 2 ) (bpy = 2,2′-bipyridine), [Ru(phen) 2 (dqtbt)](ClO 4 ) 2 ( 3 ) (phen = 1,10-phenanthroline) and [Ru(dmp) 2 (dqtbt)](ClO 4 ) 2 ( 4 ) (dmp = 2,9-dimethyl-1,10-phenanthroline) were synthesized and characterized. The cytotoxicity in vitro of the complexes was evaluated against human BEL-7402, A549, HeLa, HepG-2 and MG-63 cancer cell lines. These complexes are sensitive to BEL-7402 cells, the IC 50 values are 4.9 ± 0.5, 4.6 ± 0.4, 7.7 ± 1.8 and 1.9 ± 0.3 μM toward BEL-7402 cells. The complexes can increase the levels of reactive oxygen species and induce the decrease of mitochondrial membrane potential. Morphological and comet assay studies show that the complexes can effectively induce apoptosis in BEL-7402 cells. Complexes 1 – 4 inhibit the cell growth at G0/G1 phase in BEL-7402 cell line. The complexes can downregulate the expression of Bcl-2 and Bcl-x proteins and upregulate the levels of Bid protein in BEL-7402 cells. The results show that the complexes induce BEL-7402 cell apoptosis through a ROS-mediated mitochondrial dysfunction pathway. In addition, the complexes show strong protein-binding affinities.