Iron-Siderophore and Tumorigenesis

Iron (Fe) is an essential trace metal for the survival of all living creatures due to its inevitable role in metabolic processes including deoxyribonucleic acid (DNA) synthesis, oxygen transport, and electron transport. Human body cannot synthesize iron; therefore, it has to be taken from dietary sources. Dietary iron is absorbed in duodenum in the form of Fe²⁺ by the action of duodenal cytochrome b(DCYTB) and brings into enterocytes via divalent metal transporter 1 (DMT1). Then Fe²⁺ exits the enterocyte, facilitated by the iron efflux pump ferroportin, which combines with the oxidase hephaestin to oxidize Fe²⁺ to form Fe³⁺ and then the Fe³⁺ is loaded onto transferrin. Cancer cells exhibit elevated expression of transferrin receptor 1 (TFR1) and hepcidin and lower levels of ferroportin, which collectively lead to an increased labile iron pool. Higher concentration of iron catalyzes the production of reactive oxygen species (ROS), which consequently leads to damage to nearby proteins, carbohydrates, lipids, and DNA. Therefore, its concentration should be closely monitored. For that purpose, iron chelators such as desferoxamine, triapine, deferiprone, etc. could be used to decrease the elevated level of free iron in cancer cells.