Evaluation of anticancer activity and mechanism studies of iridium(III) polypyridyl complexes toward SK-hep1 cells

In this paper, we synthesised an organic small molecule IPD (4-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)-N,N-diphenylaniline) and its three new iridium(III) metal complexes [Ir(ppy)2(IPD)(PF6)] (Ir2a, ppy = 2-phenylpyridine), [Ir(piq)2(IPD)(PF6)] (Ir2b, piq = 1-phenylisoquinoline) and [Ir(bzq)2(IPD)(PF6)] (Ir2c, bzq = benzo[h]quinoline). After completing the synthesis and purification of the complexes, we used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method to investigate the in vitro cytotoxicity of the complexes on cancer A549, SK-hep1 and normal NIH 3T3 cells. In the dark, the complexes have no cytotoxic activity; however, upon irradiation, Ir2a and Ir2b show a high anticancer effect on inhibiting cancer proliferation of A549 and SK-hep1 cells. We explored the ability of Ir2a and Ir2b to inhibit cell proliferation and invasion by scratch and cell colony formation assays. We also detected cell cycle block, γ-H2AX, intracellular reactive oxygen levels, co-localisation and mitochondrial membrane potential, and found that Ir2a and Ir2b, located at the mitochondria, increase intracellular ROS levels, cause a decrease in mitochondrial membrane potential and induce mitochondrial dysfunction. Additionally, Ir2a and Ir2b cause apoptosis and autophagy. RNA-sequence assays suggest that Ir2a upregulates 101 genes and downregulates 143 genes. Additionally, Ir2a and Ir2b cause immunogenic cell death.