Synthesis, characterization, apoptosis, ROS, autophagy and western blotting studies of cyclometalated iridium(III) complexes

Abstract

Three iridium(III) complexes [Ir(ppy)2(DQPC)](PF6) (Ir-1), [Ir(bzq)2(DQPC)](PF6) (Ir-2) and [Ir(piq)2(DQPC)](PF6) (Ir-3) were synthesized and characterized. The cytotoxicity in vitro of the ligand DQPC and complexes Ir-1, Ir-2 and Ir-3 against cancer cells HeLa, A549, HepG2 and normal cell NIH3T3 was assessed by MTT methods. These complexes exhibit significant inhibitory effect on HeLa cells growth with an IC50 value of 2.4 ± 0.2, 2.4 ± 0.1 and 0.5 ± 0.1 µM for Ir-1, Ir-2 and Ir-3, respectively. Further studies indicated that complexes Ir-1-Ir-3 can induce apoptosis in HeLa cells and enhance the levels of intracellular ROS and Ca2+. The release of cyto-c and the changes of mitochondrial membrane potential were investigated by fluorescent microscope and flow cytometry. The effects of the complexes on DNA damage, autophagy and cell invasion were investigated under fluorescent microscope. The proportion of apoptotic and cell cycle arrest were assayed by flow cytometry. In addition, the expression levels of caspase-3 and Bcl-2 family proteins were investigated by western blot. The results show that the complexes induce apoptosis in HeLa through ROS-mediated mitochondrial dysfunction pathway.