Synthesis of ruthenium(II) complexes and investigation of their anti-proliferative mechanism against osteosarcoma cells

The objective of this study was to synthesize Ruthenium(II) complexes and investigate their anti-proliferative mechanism against osteosarcoma cells. Three ruthenium(II) polypyridyl complexes [Ru(dmb) 2(taptp)](ClO4)(2) (1), [ Ru(bpy) 2(taptp)](ClO4)(2) (2) and [Ru(phen)(2)(taptp)](ClO4)(2) (3) were synthesized and characterized. The IC50 values of 1, 2 and 3 towards MG-63 cells were 7.1 +/- 0.6, 6.4 +/- 0.4 and 8.4 +/- 0.6 mu M. These cytotoxic activities of the complexes against MG-63 cells were comparable with cisplatin under the same conditions. The complexes could effectively inhibit cell migration, induce cell cycle arrest and induce apoptosis of MG-63 cells. The complexes could enter into the cytoplasm, accumulate in the cell nuclei and induce DNA fragmentation. ROS and mitochondrial membrane potential assays demonstrated that complexes 1, 2 and 3 could increase the levels of ROS and induce the decrease of mitochondrial membrane potential. Additionally, the complexes downregulated the expression of antiapoptotic protein Bcl-x and upregulated the expression of proapoptotic protein Bid. These data indicate that the Ruthenium(II) complexes induce apoptosis of MG-63 cells through a ROS-mediated mitochondrial dysfunction pathway, which is accompanied to regulate the expression of Bcl-2 family proteins.