The Regulation and Expression of Hepcidin in Carcinogenesis as a Result of Iron Overload Disorders: An Extended Literature Review

Abstract

Aims of ProjectAs part of the research project, an extended literature review was undertaken to distinguish the relationship between hepcidin, the iron regulatory protein, and its role in the progression of carcinogenesis, based on regulation and expression in iron abundant cells. The review also aims to critically assess hepcidin's role in iron metabolism and the link between iron overload/ deficiency disorders, such as thalassemia, with the normal biological functioning of the immune system. Finally, the project aims to highlight the therapeutic uses of hepcidin in both anaemic and iron overload cancer states, with regards clinical evidence. Iron: An Introduction Biological importance of ironMaintaining Iron Concentration: Iron is the necessary molecule for cellular metabolism and is an imperative nonorganic substance, that plays a major role in oxygen transport, short-term oxygen storage [1], electron transfer [2], DNA synthesis and cell cycle phase transitioning [3]. CDK mRNA levels, for example, can be up-or down-regulated by these cell cycle control factors and triggered protein expression. Iron's physiological importance, however, is primarily determined by its oxidative state, where it has the ability to change between its ferrous (Fe2+) and ferric (Fe3+) form [4]. Thus, potentially making it a beneficial component for haemoglobin, cytochromes and several other enzymes. As well as this, iron's chemical state is important for the understanding of inorganic iron transport that is independent of transferrin [5].Iron's capability to accept and donate electrons also characterises this molecule as a toxic metal and is able to arise via the Fenton reaction, producing free radicals from converted hydrogen peroxide (H202). Thus, can cause significant damage to any proteins, DNA and fatty acids that occur within the given cell [6]. The maintenance of iron concentration is, therefore, imperative for normal biological functioning and biological systems have derived several transport and storage processes that work to achieve this homeostasis. Distribution of iron:The normal level of body iron predominantly occurs between 60-170 μg/dL [7]. Where approximately, 65 % is integrated into erythroid cells, 30% is stored within liver cell lines and bone marrow as ferritin and the remaining 5% is circulated to both myoglobin and transferrin [8]. Some circulating serum iron, however, produced by the liver must be either stored or used, to avoid the dysregulation of the bodies iron concentration [9]. Absorption of iron:Iron absorption primarily occurs in the duodenum and upper jejunum [10] and is based on a feedback mechanism that either increases or decreases iron absorption, in response to a deficient or overload state. Iron predominantly acquired from our diet is absorbed in one of two forms: as haem AbstractIron is an essential nutrient with limited bioavailability, which allows for the cell cycle progression of G1/S phases. When present in excess, iron poses a threat to cells and tissues, and therefore iron homeostasis h...