Iron is an essential metal for cellular metabolism. The reduced form of iron is a cofactor in numerous redox reactions in the cell and is therefore required for many vital physiological functions. Since iron is an oxidatively active metal, its homeostasis is tightly regulated in healthy cell. Most of iron exists in a protein-bound form, in erythrocytes as the heme compound hemoglobin, and in storage proteins such as ferritin, hemosiderin and myoglobin. Iron also is bound to proteins and non-heme enzymes involved in oxidation-reduction reactions and the transfer of electrons. There is no free iron inside the cell, however a small fraction of loosely bound iron is found in the cytoplasm. This poorly defined pool of ferrous iron is called labile iron pool. Under pathological conditions iron homeostasis may be disrupted at different levels including absorption, systemic transportation, and cellular uptake and storage. Cancer cells display dysregulated iron homeostasis and, for reasons yet poorly understood, require more iron for their metabolism and growth. As a result, in cancer cells labile iron pool is increased, and loosely bound iron catalyzes Fenton reaction and perhaps other reactions that generate reactive oxygen species. Oxygen-derived free radicals produce DNA mutations, damage proteins and lipids resulting in either cell death or cell transformation.
Keywords: Cancer; Ferroptosis; Iron addiction.
Published by Elsevier Ltd.