In vitro and in vivo anti-tumor activity of two gold(III) complexes with isoquinoline derivatives as ligands.
Eur J Med Chem
; 163: 333-343, 2019 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-30529636
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-24â¯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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Ouro
/
Isoquinolinas
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Antineoplásicos
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article