Indexed on: 09 Nov '16Published on: 04 Nov '16Published in: Journal of Inorganic Biochemistry
The alkynyl gold(I) derivative [Au(C ≡ CPh)(PTA)] (PTA = 1,3,5-triaza-7-phosphaadamantane) induces apoptosis in colorectal carcinoma tumour cells (Caco-2) without affecting to normal enterocytes. [Au(C ≡ CPh)(PTA)] is a slight lipophilic drug, stable in PBS (Phosphate Buffered Saline) and able to bind BSA (Bovin Serum Albumin) by hydrophobic interactions. Once inside the cell, [Au(C ≡ CPh)(PTA)] targets seleno proteins such as Thioredoxin Reductase 1, increasing ROS (Reactive Oxygen Species) levels, reducing cell viability and proliferation and inducing mitochondrial apoptotic pathway, pro-apoptotic and anti-apoptotic protein imbalance, loss of mitochondrial membrane potential, cytochrome c release and activation of caspase 9 and 3. Moreover, unlike other metal-based drugs such as cisplatin, [Au(C ≡ CPh)(PTA)] does not target nucleic acid, reducing the risk of side mutation in the DNA. In consequence, our results predict a promising future for [Au(C ≡ CPh)(PTA)] as a chemotherapeutic agent for colorectal carcinoma.