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

Two gold(III) complexes of isoquinoline derivatives: [Au(L-1)Cl-2] (Au1) and [Au(L-2)Cl-2] (Au2) have been prepared and characterized. Aul 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. (C) 2018 Elsevier Masson SAS. All rights reserved.