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

Three Ru(II) polypyridyl complexes [Ru(dmb) 2 (HMSPIP)](ClO 4 ) 2 ( 1 ), [Ru(phen) 2 (HMSPIP)](ClO 4 ) 2 ( 2 ) and [Ru(dmp) 2 (HMSPIP)](ClO 4 ) 2 ( 3 ) were synthesized and characterized. The cytotoxicity in vitro, apoptosis, cell cycle arrest, reactive oxygen species and mitochondrial membrane potential were assayed. The IC 50 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.