DNA interaction, cytotoxicity, apoptotic activity, cell cycle arrest, reactive oxygen species and mitochondrial membrane potential assay induced by ruthenium(II) polypyridyl complexes
Abstract Our previous studies showed that ruthenium(II) polypyridyl complexes can suppress the proliferation of BEL-7402 and MG-63 cells. In the present study, two active complexes Ru-1 and Ru-2 were identified to effectively inhibit BEL-7402, HeLa, MCF-7 and MG-63 cells growth. The cytotoxicity in vitro of the complexes towards the above cell lines were evaluated by MTT assay. The IC50 values range from 5.1 to 18.5 μM. Complex Ru-2 shows higher cytotoxic activity than cisplatin towards selected cell lines under identical conditions. AO/EB and Hoechst 33258 staining and flow cytometry analyses indicate that Ru-1 and Ru-2 can induce apoptosis in BEL-7402 cells. In the assay of cell cycle arrest, Ru-2 can induce G0/G1 phase arrest on BEL-7402 cells. The two complexes can enhance the level of ROS and decrease the mitochondrial membrane potential. Ru-1 and Ru-2 induced apoptosis in BEL-7402 cells through the mitochondrial pathway. In addition, the DNA-binding of these complexes with calf thymus was also investigated.