Anticancer Activities of Ferrous and Ferric Ions in Progression, Proliferation, Angiogenesis, Invasion and Metastasis against Cancer and Tumor Cells

The process of ferroptotic death is characterized by the overwhelming, iron-depending accumulation of lethal lipid ROS. Unlike other forms of apoptotic and non-apoptotic death, this requirement for ROS accumulation appears to be universal. Redox cycling is a characteristic of transition metals such as iron (Ferritin Fe3+ ⇄ Ferrous Fe2+). Iron via the Fenton reaction can exacerbate the consequences of hydrogen peroxide (H2O2) production, leading to the generation of hydroxyl radicals. The superoxide ion can participate in regenerating ferrous iron that is required for the Fenton reaction. An excess of iron is toxic due to its ability to engage in redox cycling and promote free radical formation. Super oxide anion generation; O2 → ･O2－. Hydrogen peroxide production; ･O2－ + 2H+ + e- → H2O2. Haber-Weiss reaction; H2O2 + O2－ → ･OH + OH－ + O2. Fenton reaction; Fe2+ + H2O2 → Fe3+ + OH－ + ･OH. Reduction to Fe(Ⅱ); Fe3+ ＋ ･O2－ → Fe2+ + O2. Ferritin is stable in iron-rich conditions, whereas it is rapidly degraded under conditions of iron starvation and ferritin degradation can be led. New blood vessel formation in angiogenesis is fundamental to tumor growth, invasion, and metastatic dissemination. Iron deficiency will lead to the dysfunction of immune system, metabolic disorders, myasthenia and anemia, whereas, excess iron also damages several vital organs. Thus, iron is essential for multiple cell functions, but is also potentially deleterious reasons of its ability to generate free oxygen radicals, iron balance by continuously recycling and reusing cellular iron, storage in ferritin, and export through ferroportin protecting cells from free iron toxicity. However. the exact molecular mechanism involved on iron imbalance in development for tumor cells and the iron overload-mediated induction of apoptosis are required to be explored in future.