Cellular iron homeostasis and therapeutic implications of iron chelators in cancer

Iron metabolism and homeostasis are imperative for the maintenance of normal physiological activities due to the element's critical involvement in a wide variety of crucial biological processes like cellular respiration, metabolic pathways, DNA replication, repair, detoxification, neurotransmission and cellular signaling. Being a key contributor of crucial machineries regulating cellular proliferation and survival, it facilitates the process of tumor growth and development. Thus, tumor cells strive to acquire higher amount of iron than non-malignant cells to satisfy their elevated rate of metabolism. Perhaps, not surprisingly chelation of this metal ion was thought to be effective in treating cancer, but due to a variety of side effects, the use of iron chelators was clinically insignificant. However, discovery of various new classes of iron chelators with lesser side effects and selective toxicity towards cancer cells has revived the possibilities of using iron chelators in anti-cancer therapy. In this review, we have discussed the role of iron in promoting malignant mechanisms and the prospects of usage of different classes of iron chelators in cancer therapeutics.