Oxidative Stress Mechanism by Gold Compounds: A Close Look at Total ROS Increase and the Inhibition of Antioxidant Enzymes.

Abstract

The antitumor activity of various gold compounds is a promising field of investigation, attracting researchers seeking potential clinical candidates. To advance this research, they explore the complex mechanisms of action of these compounds. Since the discovery of the strong inhibition of thioredoxin reductase by auranofin, the primary mechanism explored has been the inhibition of this enzyme. This inhibition disrupts the redox balance in cells, promoting oxidative stress and triggering cell death. In this review, we analyzed studies from the past decade that measured cellular ROS increase and examined the coordination structures of gold compounds. We also correlate ROS increase with the inhibition of redox-regulating enzymes, thioredoxin reductase, and glutathione reductase, to elucidate the relationship between these cellular effects and chemical structures. Our data compilation reveals that different structures exhibit varying efficacy: some significantly increase ROS production and inhibit thioredoxin reductase or glutathione reductase, while others elevate ROS levels without affecting these target enzymes, suggesting alternative mechanisms of action. This review consolidates critical evidence, enhancing our understanding of the mechanisms by which these gold complexes act and providing valuable insights for developing new therapeutic strategies against tumor cells.