Targeting Free Radicals in Oxidative Stress-Related Human Diseases

• Published in: Trends in pharmacological sciences (Regular ed.) Vol. 38; no. 7; pp. 592 - 607
• Main Authors: Poprac, Patrik, Jomova, Klaudia, Simunkova, Miriama, Kollar, Vojtech, Rhodes, Christopher J, Valko, Marian
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2017
• Subjects: Advanced Basic Science; Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Alzheimer’s disease; antioxidants; Antioxidants - pharmacology; cancer; Chelating Agents - pharmacology; Free Radical Scavengers - pharmacology; Free Radicals - metabolism; Humans; Neoplasms - drug therapy; Neoplasms - metabolism; oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Reactive Oxygen Species - metabolism; ROS; cancer; Alzheimer’s disease; antioxidants; oxidative stress; ROS
• ISSN: 0165-6147; 1873-3735
• DOI: 10.1016/j.tips.2017.04.005

Cancer and Alzheimer’s disease (AD) are characterized by (i) opposing biological mechanisms, (ii) an inverse correlation between their incidences, and (iii) oxidative stress being a common denominator of both diseases. Increased formation of reactive oxygen species (ROS) in cancer cells from oncogenic signaling and/or metabolic disturbances leads to upregulation of cellular antioxidant capacity to maintain ROS levels below a toxic threshold. Combining drugs that induce high levels of ROS with compounds that suppress cellular antioxidant capacity by depleting antioxidant systems [glutathione (GSH), superoxide dismutase (SOD), and thioredoxin (TRX)] and/or targeting glucose metabolism represents a potential anticancer strategy. In AD, free metals and/or Aβ:metal complexes may cause damage to biomolecules in the brain (via Fenton reaction), including DNA. Metal chelation, based on the application of selective metal chelators or metal delivery, may induce neuroprotective signaling and represents a promising therapeutic strategy. This review examines therapeutic strategies based on the modulation of oxidative stress in cancer and AD.