Abstract
An iridium(III) complex [Ir(ppy)2(MHPIP)]PF6 (ppy = 2-phenylpyridine, MHPIP = 2-(1-methyl-1H-pyrazol-3-yl)-1H-imidazo[4,5-f][1, 10]phenanthroline, Ir-1) was synthesized and characterized by elemental analysis, IR, 1H NMR and 13C NMR. The in vitro cytotoxic activities of the free proligand MHPIP and the complex Ir-1 against HepG2, A549, BEL-7402, SGC-7901 and normal LO2 cells were evaluated by the MTT method. MHPIP has no cytotoxic activity toward the selected cell lines, while Ir-1 shows a moderate cytotoxic effect against HepG2. This complex also displays no cytotoxicity against normal LO2 cells, with an IC50 of more than 200 µM. The apoptosis of HepG2 cells induced by the complex was studied with AO/EB and DAPI staining methods, which showed that the complex can effectively induce apoptosis. A comet assay was performed by gel electrophoresis, and the results further show that the complex can cause apoptosis. The level of reactive oxygen species, mitochondrial membrane potential, autophagy, intracellular Ca2+ levels and cell invasion were investigated by fluorescence microscopy, and the cell cycle arrest was studied by flow cytometry. The expression of caspase and Bcl-2 family proteins was investigated by western blot. The results of these experiments indicate that Ir-1 accumulates preferentially in the mitochondria of HepG2 cells and induces apoptosis through inhibition of the PI3K/AKT/mTOR pathway.
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