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

TitleIn vitro and in vivo anti-tumor activity of two gold(III) complexes with isoquinoline derivatives as ligands
Publication TypeJournal Article
Year of Publication2019
AuthorsKhan, T-M, Gul, NShad, Lu, X, Wei, J-H, Liu, Y-C, Sun, H, Liang, H, Orvig, C, Chen, Z-F
JournalEurop. J. Med. Chem.
Volume163
Pagination333 - 343
ISSN0223-5234
KeywordsANTITUMOR ACTIVITY, Cell apoptosis, Gold(III) complexes, Isoquinoline, Mitochondrial dysfunction
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.

URLhttp://www.sciencedirect.com/science/article/pii/S0223523418310067
DOI10.1016/j.ejmech.2018.11.047