Redox cycling metals: Pedaling their roles in metabolism and their use in the development of novel therapeutics

Kalinowski, D.S, Stefani, C., Toyokuni, S., Ganz, T., Anderson, G.J., Subramaniam, V.N., Trinder, D., Olynyk, J.K., Chua, A., Jansson, P.J., Sahni, S., Lane, D.J.R., Merlot, A.M., Kovacevic, Z., Huang, M.L.H., Lee, C.S., & Richardson, D. (2016) Redox cycling metals: Pedaling their roles in metabolism and their use in the development of novel therapeutics. Biochimica et Biophysica Acta - Molecular Cell Research, 1863(4), pp. 727-748.

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Essential metals, such as iron and copper, play a critical role in a plethora of cellular processes including cell growth and proliferation. However, concomitantly, excess of these metal ions in the body can have deleterious effects due to their ability to generate cytotoxic reactive oxygen species (ROS). Thus, the human body has evolved a very well-orchestrated metabolic system that keeps tight control on the levels of these metal ions. Considering their very high proliferation rate, cancer cells require a high abundance of these metals compared to their normal counterparts. Interestingly, new anti-cancer agents that take advantage of the sensitivity of cancer cells to metal sequestration and their susceptibility to ROS have been developed. These ligands can avidly bind metal ions to form redox active metal complexes, which lead to generation of cytotoxic ROS. Furthermore, these agents also act as potent metastasis suppressors due to their ability to up-regulate the metastasis suppressor gene, N-myc downstream regulated gene 1. This review discusses the importance of iron and copper in the metabolism and progression of cancer, how they can be exploited to target tumors and the clinical translation of novel anti-cancer chemotherapeutics.

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13 citations in Scopus
10 citations in Web of Science®
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ID Code: 99743
Item Type: Journal Article
Refereed: Yes
Keywords: 3 aminopicolinaldehyde thiosemicarbazone; antineoplastic agent; benzoylpyridine thiosemicarbazone derivative; bis(thiosemicarbazone) derivative; copper; deferoxamine; di 2 pyridylketone 4 cyclohexyl 4 methyl 3 thiosemicarbazone; di 2 pyridylketone 4, 4 dimethyl 3 thiosemicarbazone; di 2 pyridylketone thiosemicarbazone derivative; glyoxal bis(n4 methyl 3 thiosemicarbazone); hepcidin; iron; metal; metal complex; metal ion; reactive oxygen metabolite; thiosemicarbazone derivative; unclassified drug; anti, angiogenesis; antineoplastic activity; antiproliferative activity; cancer therapy; carcinogenesis; cell cycle; copper metabolism; DNA synthesis; drug targeting; gene expression; human; iron metabolism; iron storage; iron transport; ligand binding; metabol, Animals; Antineoplastic Agents; Chelating Agents; Copper; Drug Discovery; Humans; Iron; Metals; Neoplasms; Oxidation-Reduction; Reactive Oxygen Species
DOI: 10.1016/j.bbamcr.2016.01.026
ISSN: 1879-2596
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Copyright Owner: © 2016 Elsevier B.V.
Deposited On: 12 Oct 2016 00:43
Last Modified: 12 Oct 2016 23:05

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