Copper-mediated reactive oxygen species generation

Copper-mediated reactive oxygen species (ROS) generation is a biochemical process where copper ions participate in redox cycling to produce highly reactive free radicals, such as hydroxyl radicals, through Fenton-like and Haber-Weiss reactions [1, 3]. In these reactions, copper cycles between its Cu(I) and Cu(II) oxidation states, reacting with hydrogen peroxide to cause significant oxidative damage to cellular lipids, proteins, and DNA [3, 6]. In a therapeutic context, this mechanism is exploited to induce selective cytotoxicity in cancer cells, which often exhibit altered copper metabolism and higher basal oxidative stress compared to healthy cells [5]. Drugs like copper ionophores, including elesclomol and disulfiram, increase intracellular copper concentrations to trigger ROS-dependent cell death pathways, such as apoptosis and the recently identified cuproptosis [2, 5]. Conversely, dysregulated copper-mediated ROS generation is a primary pathological driver in conditions like Wilson's disease and certain neurodegenerative disorders [4, 6]. In these diseases, the accumulation of free copper leads to chronic oxidative stress and tissue damage, particularly in the liver and brain [4]. Therapeutic strategies for these conditions involve the use of copper chelators, such as D-penicillamine, to sequester copper and mitigate oxidative cascades [4]. Overall, the modulation of copper-mediated ROS generation represents a delicate balance between inducing targeted cell death in oncology and preventing systemic toxicity in metabolic or degenerative diseases [5, 6].

Other names

Copper-induced oxidative stressCopper-catalyzed ROS productionCopper-dependent ROS generationFenton-like reaction (copper-based)

Copper ionophores facilitate intracellular copper accumulation, leading to redox cycling and the production of hydroxyl radicals via Fenton-like reactions, which induce oxidative damage and cell death.