Ruthenium(II) polypyridyl complexes: synthesis, cytotoxicity in vitro, reactive oxygen species, mitochondrial membrane potential and cell cycle arrest studies

Two Ru(II) polypyridyl complexes [Ru(dmb) 2 (idpq)](ClO 4 ) 2 ( 1 ) (idpq = indeno[1,2- b ]dipyrido[3,2- f :2′,3′- h ]-quinoxaline-6-one, dmb = 4,4′-dimethyl-2,2′-bipyridine) and [Ru(bpy) 2 (idpq)](ClO 4 ) 2 ( 2 ) (bpy = 2,2′-bipyridine) have been synthesized and characterized. Their in vitro cytotoxicities, apoptosis, cellular uptake, production of reactive oxygen species (ROS), mitochondrial membrane potential assays and effects on cell cycle distribution were studied. The IC 50 values range from 13.1 ± 1.1 to 30.9 ± 3.1 μM. Complex 1 is toxic to HeLa cells with an IC 50 value of 13.1 ± 1.1 μM, while complex 2 shows relatively high cytotoxicity against HepG-2 cells. However, both complexes exhibit lower cytotoxicity than cisplatin toward selected cell lines under identical conditions. Both complexes can induce apoptosis and cell cycle arrest at the S and G0/G1 phases in HeLa cells, respectively. In addition, both Ru(II) complexes, which can be effectively taken up by HeLa cells, induced generation of intracellular ROS in a concentration-dependent manner and produced a decrease in mitochondrial membrane potential. The results show that these complexes induce apoptosis in HeLa cells through a ROS-mediated mitochondrial dysfunction pathway.