Iron Chelators for the Treatment of Cancer

ironjustice@aol.com · medicine forum Guru Joined: 28 Apr 2005 Posts: 1522

Molecular Mechanisms of Iron Uptake by Cells and the Use of Iron
Chelators for the Treatment of Cancer
Des R. Richardson

The field of iron (Fe) metabolism has been invigorated in the past 10
years with the discovery of a variety of new molecules involved in the
homeostatic control of this critical nutrient. These proteins include
the transferrin receptor 2, frataxin, hephaestin, hepcidin, hemojuvelin
and others. Basic understanding of the metabolism of Fe in cells is
vital in order to develop Fe chelators for the treatment of a variety
of disease states. In addition, examination of the role of Fe in the
regulation of cell cycle progression and angiogenesis has led to
investigations of the use of novel Fe chelators as anti-proliferative
agents. These studies have resulted in the identification of new
ligands that show selective and potent anti-tumor activity in vitro and
in vivo. Moreover, the ability of these chelators to inhibit growth is
not only limited to the inhibition of DNA synthesis. In fact, there is
a range of targets that are affected by Fe-depletion, such as molecules
involved in cell cycle control, angiogenesis and metastasis
suppression. These include hypoxia-inducible factor-1a (HIF-1a),
vascular endothelial growth factor-1 (VEGF1), p21CIP1/WAF1, cyclin D1
and the protein product of the N-myc downstream regulated gene-1
(Ndrg1). As such, Fe chelators can now be designed to target molecules
to induce specific effects, for instance, angiogenesis or metastasis
suppression.

http://bentham.org/cmc/contabs/cmc12-23.htm#6

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