|Title||In vitro and in vivo anti-tumor activity of two gold(III) complexes with isoquinoline derivatives as ligands|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Khan, T-M, Gul, NShad, Lu, X, Wei, J-H, Liu, Y-C, Sun, H, Liang, H, Orvig, C, Chen, Z-F|
|Journal||Europ. J. Med. Chem.|
|Pagination||333 - 343|
|Keywords||ANTITUMOR ACTIVITY, Cell apoptosis, Gold(III) complexes, Isoquinoline, Mitochondrial dysfunction|
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.