Photoinduced ROS regulation of apoptosis and mechanism studies of iridium(iii) complex against SGC-7901 cells

Abstract

A new iridium(III) complex, [Ir(ppy)₂(FBPIP)]PF₆ (Ir-1), was synthesized and characterized. The cytotoxic activity of this complex against SGC-7901, PC-12, SiHa, HepG2, BEL-7402, A549, HeLa and normal LO2 cells was investigated using the MTT method. The complex showed no cytotoxic activity against the selected cell lines. However, upon irradiation, the complex displayed potent anti-proliferative activity toward SGC-7901 cells, with a low IC₅₀ value of 6.1 ± 0.6 μM, and showed selectivity between cancer and normal cells. Apoptosis was assayed using the AO/EB staining method. The level of reactive oxygen species (ROS), mitochondrial membrane potential, autophagy and cell invasion were studied under a fluorescence microscope. The cell cycle distribution was studied by flow cytometry. The expression of caspase and Bcl-2 family proteins was investigated by western blot. Complex Ir-1 was shown to accumulate preferentially in the mitochondria of SGC-7901 cells and induced apoptosis via the mitochondrial pathway, which involved ROS generation, mitochondrial membrane potential depolarization, and Bcl-2 and caspase family member activation. These results demonstrate that the complex induces cancer cell apoptosis by acting on mitochondrial pathways.