The anticancer effect related to disturbances in redox balance on Caco-2 cells caused by an alkynyl gold(I) complex.

Abstract

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 caspases 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.

• Authors: Cristina Sánchez-de-Diego, Inés Mármol, Rocío Pérez, Sonia Gascón, Mª Jesús Rodriguez-Yoldi, Elena Cerrada
• Journal: Journal of inorganic biochemistry (J Inorg Biochem) Vol. 166 Pg. 108-121 (01 2017) ISSN: 1873-3344 [Electronic] United States
• PMID: 27842247 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Coordination Complexes
• Neoplasm Proteins
• Serum Albumin, Bovine
• Gold
• Cytochromes c
• TXNRD1 protein, human
• Thioredoxin Reductase 1
• CASP3 protein, human
• CASP9 protein, human
• Caspase 3
• Caspase 9

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis (drug effects)
• Caco-2 Cells
• Caspase 3 (metabolism)
• Caspase 9 (metabolism)
• Cattle
• Colorectal Neoplasms (drug therapy, metabolism)
• Coordination Complexes (chemistry, pharmacology)
• Cytochromes c (metabolism)
• Gold (chemistry, pharmacology)
• Humans
• Membrane Potential, Mitochondrial (drug effects)
• Neoplasm Proteins (metabolism)
• Oxidation-Reduction (drug effects)
• Serum Albumin, Bovine (chemistry)
• Thioredoxin Reductase 1 (metabolism)