Novel cyclometalated iridium(iii) phosphine-imine (P^N) complexes: highly efficient anticancer and anti-lung metastasis agents in vivo†
Herein, a new class of iridium(III)-based metal complexes with phosphine-imine (P^N) ligands are synthesized and authenticated. These complexes show high cytotoxicities against seven cancer cells in vitro. Simultaneously, antitumor mechanism studies show that complex Ir3 induces apoptosis by depolarization of mitochondrial membrane potential, ROS overproduction and ROS-mediated DNA damage. Importantly, BIX01294, a G9a histone methyltransferase inhibitor, could markedly sensitize Ir3-induced cytotoxicity, cell cycle arrest, apoptosis and inhibition of migration in HCT116 cancer cells in vitro. Finally, we show that combined treatment with Ir3 and BIX01294 potently inhibits tumour growth and lung metastasis in vivo. Taken together, we demonstrate that BIX01294 could potently sensitize iridium(III)-based metal complex-induced inhibition of tumour progression and provide the basis for developing new metal-based anticancer agents and therapeutic strategies in vivo for effective cancer therapy.