Cytotoxicity, apoptosis, cell cycle arrest, reactive oxygen species, mitochondrial membrane potential, and Western blotting analysis of ruthenium(II) complexes

Three new ruthenium(II) complexes—[Ru(bpy) 2 (adppz)](ClO 4 ) 2 , [Ru(dmb) 2 (adppz)](ClO 4 ) 2 , and [Ru(dmp) 2 (adppz)](ClO 4 ) 2 (bpy is 2,2′-bipyridine, adppz is 7-aminodipyrido[3,2- a :2′,3′- c ]phenazine, dmb is 4,4′-dimethyl-2,2′-bipyridine, and dmp is 2,9-dimethyl-1,10-phenanthroline)—were synthesized. [Ru(dmp) 2 (adppz)](ClO 4 ) 2 exhibits higher cytotoxicity than cisplatin toward A549, MG-63, and SKBR-3 cells. The apoptosis and cellular uptake were studied by fluorescence microscopy. [Ru(dmp) 2 (adppz)](ClO 4 ) 2 enhances the level of reactive oxygen species (ROS) and decreases the mitochondrial membrane potential. These complexes induce cell cycle arrest in S phase in BEL-7402 cells, and inhibit the antiproliferation of SKBR-3 cells at G 0 /G 1 phase. Western blotting analysis shows that [Ru(dmp) 2 (adppz)](ClO 4 ) 2 induces apoptosis in BEL-7402 cells through activation of caspase 3, caspase 7, and procaspase 7 and ROS-mediated mitochondrial dysfunction pathways. Graphical abstract