Selenium Metabolic Pathway in Ferroptotic Cell Death

Selenoproteins play a crucial role in various complex biological processes, including cell growth, differentiation, apoptosis, and ferroptosis. In response to increased oxidative damage and altered nutrient metabolism known as the Warburg switch, cancer cells adapt via selenoprotein synthesis that are essential for their survival. Especially, selenoprotein thioredoxin reductase 1 (TrxR1) and glutathione peroxidase-4 (GPX4) have significant roles in controlling hydroperoxides and resisting ferroptosis. These selenoproteins offer protection to cancer cells from ferroptosis and oxidative damage by utilizing selenium-related mechanisms to counteract the toxic effects of chemotherapy and radio-therapy. The bioavailability of selenium is often overlooked as a determinant of oxidative defense status and has emerged as a critical factor in cancer cells. Hence, the impact of dietary selenium depletion in the context of anticancer treatment highlighted the need for further investigation into the potential therapeutic applications of selenium or selenoproteins in cancer treatment. This chapter explores the potential application of selenoproteins as therapeutic targets in cancer treatment, with a specific focus on ferroptosis.