Role of Selenium as an Antioxidant in Cancer Prevention: A Review

Selenium is a crucial trace element integrated into selenoproteins such as glutathione peroxidases (GPxs), thioredoxin reductases (TrxRs), and selenoprotein P (SELENOP), which preserve redox homeostasis by neutralizing reactive oxygen species (ROS) and preventing lipid peroxidation, thus alleviating oxidative stress associated with carcinogenesis. This review clarifies selenium’s biochemistry, encompassing selenocysteine biosynthesis and integration through SECIS elements, as well as its modulation of the Nrf2 pathway for antioxidant gene expression, highlighting its intricate dual roles in normal cytoprotection versus potential cancer promotion under chronic activation. Experimental evidence from in vitro, animal, and epidemiological studies illustrates anticancer effects through apoptosis induction (via p53/Bcl-2/caspase pathways), cell cycle arrest, antiangiogenesis, epigenetic regulation (DNA demethylation and histone modifications), and immune modulation. Clinical trials such as SELECT and NPC emphasize benefits predominantly in selenium-deficient populations utilizing organic forms like selenomethionine rather than inorganic selenite. Optimal bioavailability differs by form of organic compounds, such as methylselenocysteine demonstrate enhanced absorption and reduced toxicity, while novel selenium nanoparticles improve targeted delivery, highlighting selenium’s potential in cancer prevention strategies customized to genetic and nutritional profiles.