In vitro and in vivo anti-tumor activity of two gold(III) complexes with isoquinoline derivatives as ligands

Abstract

Two gold(III) complexes of isoquinoline derivatives: [Au(L¹)Cl₂] (Au1) and [Au(L²)Cl₂] (Au2) have been prepared and characterized. Au1 and Au2 exhibited greater cytotoxicity than their corresponding ligands and cisplatin against T-24 cells. Both complexes arrested cell cycle at S-phase by upregulation of p53, p27, and p21, and downregulation of cyclin A and cyclin E. The depolarization of the mitochondrial membrane potential, generation of ROS, and stimulated Ca²⁺ release activated the caspase cascade and ultimately caused apoptosis by increasing the levels of Bax and Bak, and decreasing the levels of Bcl-2 and Bcl-xl. Cell apoptosis was achieved via mitochondria mediated pathways. The in vivo studies of Au1 and Au2 demonstrated that they were safer than cisplatin and could effectively inhibit tumor growth.

Keywords: Antitumor activity; Cell apoptosis; Gold(III) complexes; Isoquinoline; Mitochondrial dysfunction.