Redox Homeostasis and Metabolism in Cancer: A Complex Mechanism and Potential Targeted Therapeutics

• Published in: International journal of molecular sciences 2020-04, Vol.21 (9), p.3100
• Main Authors: Ghoneum, Alia, Abdulfattah, Ammar Yasser, Warren, Bailey Olivia, Shu, Junjun, Said, Neveen
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Antioxidants; Biological activity; Cancer; Carcinogens; Cell cycle; Clinical Trials as Topic; Cytochrome; Cytokines; Deoxyglucose; Deoxyribonucleic acid; Disease Progression; DNA; Enzymes; Free radicals; Gene expression; Growth factors; HIF-1α; Homeostasis; Homeostasis - drug effects; Humans; Hypoxia; Immune system; Kinases; Metabolic Networks and Pathways - drug effects; Metabolic pathways; Metabolism; Metastases; Mitochondria; Mitochondrial DNA; Molecular Targeted Therapy; Mutation; Neoplasms - drug therapy; Neoplasms - metabolism; Nitrogen dioxide; Oxidation; Oxidative stress; Oxidative Stress - drug effects; PGC-1α; Phenotypes; Phosphorylation; Physiology; Production increases; Proteins; Reactive oxygen species; Reactive Oxygen Species - metabolism; redox systems; Respiration; Review; ROS; Signal Transduction - drug effects; Therapeutic targets; Transcription; Tumors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21093100

Reactive Oxygen Species or "ROS" encompass several molecules derived from oxygen that can oxidize other molecules and subsequently transition rapidly between species. The key roles of ROS in biological processes are cell signaling, biosynthetic processes, and host defense. In cancer cells, increased ROS production and oxidative stress are instigated by carcinogens, oncogenic mutations, and importantly, metabolic reprograming of the rapidly proliferating cancer cells. Increased ROS production activates myriad downstream survival pathways that further cancer progression and metastasis. In this review, we highlight the relation between ROS, the metabolic programing of cancer, and stromal and immune cells with emphasis on and the transcription machinery involved in redox homeostasis, metabolic programing and malignant phenotype. We also shed light on the therapeutic targeting of metabolic pathways generating ROS as we investigate: Orlistat, Biguandes, AICAR, 2 Deoxyglucose, CPI-613, and Etomoxir.