Apoptosis in BEL-7402 cells induced by ruthenium(II) complexes through a ROS-mediated mitochondrial pathway

Abstract

Three Ru(II) polypyridyl complexes [Ru(dmb)2(HMSPIP)](ClO4)2 (1), [Ru(phen)2(HMSPIP)](ClO4)2 (2) and [Ru(dmp)2(HMSPIP)](ClO4)2 (3) were synthesized and characterized. The cytotoxicity in vitro, apoptosis, cell cycle arrest, reactive oxygen species and mitochondrial membrane potential were assayed. The IC50 values of complexes 1, 2 and 3 toward BEL-7402, A549, MG-63 and SK-BR-3 cell lines ranged from 10.9 ± 1.6 to 42.0 ± 3.4 μM. Complexes 1, 2 and 3 can effectively induce apoptosis and inhibit the growth of BEL-7402 cells at the G2/M phase. These complexes can enhance the level of reactive oxygen species and induce decrease in the mitochondrial membrane potential. Additionally, complex 2 can down-regulate the expression of antiapoptotic protein of Bcl-2 protein and up-regulate the levels of proapoptotic protein Bim in BEL-7402 cells.