Novel cyclometalated iridium(iii) phosphine-imine (P^N) complexes: highly efficient anticancer and anti-lung metastasis agents in vivo. Issue 5 (11th February 2020)

• Record Type: Journal Article
• Authors: Xu, Zhishan; Yang, Yuliang; Jia, Xianglei; Guo, Lihua; Ge, Xingxing; Zhong, Genshen; Chen, Shujiao; Liu, Zhe
• Is Part Of: Inorganic chemistry frontiers. Volume 7:Issue 5(2020)
• Page Start: 1273
• Page End: 1283
• Publication Date: 2020-02-11
• Subjects: Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/c9qi01492f
• Languages: English
• ISSNs: 2052-1553

Abstract

Abstract : Iridium(iii )-based complexes with phosphine-imine (P^N) ligands are synthesized and authenticated. The combined treatment with Ir(iii ) and BIX01294 potently inhibited tumour growth and lung metastasis in vitro and in vivo . Abstract : 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.