Abstract
Superoxide dismutases (SODs) are critical metalloenzymes involved in detoxifying reactive oxygen species (ROS), playing a pivotal role in maintaining redox homeostasis and cellular integrity. Comprising three isoforms—SOD1 (cytosolic Cu/Zn-SOD), SOD2 (mitochondrial Mn-SOD), and SOD3 (extracellular Cu/Zn-SOD)—these enzymes catalyze the dismutation of superoxide radicals into hydrogen peroxide and oxygen. Altered SOD expression and function are closely linked to cancer initiation, progression, metastasis, and therapy resistance. SOD1 and SOD2 promote tumor survival by regulating redox-sensitive signaling pathways, including MAPK, PI3K/Akt, and NF-κB. The mTORC1-SOD1 axis emerges as a key mediator of cancer cell adaptation to hypoxia and nutrient deprivation. SOD2 overexpression enhances redox signaling and tumorigenicity, while its inhibition sensitizes tumors to chemotherapeutic agents like 5-fluorouracil. SOD3, traditionally viewed as protective, shows dual roles depending on the cancer context, with implications in angiogenesis, metastasis, and prognosis. Moreover, synthetic MnSOD mimetics—such as Mn porphyrins, salens, and mitochondrial-targeted antioxidants—offer therapeutic potential by modulating oxidative stress in tumor microenvironments, acting as both radiosensitizers and radioprotectors. These findings highlight the multifaceted functions of SOD enzymes in cancer biology and underscore their value as diagnostic biomarkers and therapeutic targets in redox-based cancer treatment strategies.
Keywords
References
The published articles will be distributed under the Creative Commons Attribution 4.0 International License (CC BY). It is allowed to copy and redistribute the material in any medium or format, and remix, transform, and build upon it for any purpose, even commercially, as long as appropriate credit is given to the original author(s), a link to the license is provided and it is indicated if changes were made. Users are required to provide full bibliographic description of the original publication (authors, article title, journal title, volume, issue, pages), as well as its DOI code. In electronic publishing, users are also required to link the content with both the original article published in Journal of Medical Biochemistry and the licence used.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.