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

Abstract

Three new ruthenium(II) complexes-[Ru(bpy)2(adppz)](ClO4)2, [Ru(dmb)2(adppz)](ClO4)2, and [Ru(dmp)2(adppz)](ClO4)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)](ClO4)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)](ClO4)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 G0/G1 phase. Western blotting analysis shows that [Ru(dmp)2(adppz)](ClO4)2 induces apoptosis in BEL-7402 cells through activation of caspase3, caspase7, and procaspase 7 and ROS-mediated mitochondrial dysfunction pathways.