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Metallo-Drugs: Development and Action of Anticancer Agents

Ed. by Sigel, Astrid / Sigel, Helmut / Freisinger, Eva / Sigel, Roland K.O.

With contrib. by Riddell, Imogen / Lippard, Stephen J. / Brabec, Victor / Kasparkova, Jana / Menon, Vijay / Farrell, Nicholas P. / Venkatesh, V. / Sadler, Peter J. / Gorle, Anil K. / Peterson, Erica J. / Berners-Price, Susan / Alessio, Enzo / Messori, Luigi / Babak, Maria V. / Ang, Wee Han / Casini, Angela / Sun, Raymond Wai-Yin / Ott, Ingo / Tshuva, Edit / Miller, Maya / Crans, Debbie / Yan, Lining / Haase, Allison / Yang, Xiaogai / Chitambar, Christopher / Cardo, Lucia / Hannon, Michael John / Vilar, Ramon / Sullivan, Matthew P. / Holtkamp, Hannah U. / Hartinger, Christian G. / Schatzschneider, Ulrich / Thévenod, Frank / Denoyer, Delphine / Clatworthy, Sharnel A. S. / Cater, Michael / Ziliotto, Silvia / Ogle, Olivia / Taylor, Kathryn M.

Series:Metal Ions in Life Sciences 18

eBook (PDF)
Publication Date:
February 2018
Copyright year:
2018
ISBN
978-3-11-047073-4
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15. Iron and Its Role in Cancer Defense: A Double-Edged Sword

Thévenod, Frank

Abstract

Iron (Fe) is an essential metal, vital for biological functions, including electron transport, DNA synthesis, detoxification, and erythropoiesis that all contribute to metabolism, cell growth, and proliferation. Interactions between Fe and O2 can result in the generation of reactive oxygen species (ROS), which is based on the ability of Fe to redox cycle. Excess Fe may cause oxidative damage with ensuing cell death, but DNA damage may also lead to permanent mutations. Hence Fe is carcinogenic and may initiate tumor formation and growth, and also nurture the tumor microenvironment and metastasis. However, Fe can also contribute to cancer defense. Fe may induce toxic ROS and/or initiate specific forms of cell death, including ferroptosis that will benefit cancer treatment. Furthermore, Fe-binding and Fe-regulatory proteins, such as hepcidin, lipocalin-2/NGAL, heme oxygenase-1, ferritin, and iron-sulfur clusters can display antitumor properties under specific conditions and in particular cancer types. In addition, the milk protein lactoferrin may synergize with other established anticancer agents in the prevention and therapy of cancer. Consequently, drugs that target Fe metabolism in tumors are promising candidates for the prevention and therapy of cancer, but consideration of context specificity (e.g., tumor type; systemic versus tumor microenvironment Fe homeostasis) is mandatory.

Citation Information

Frank Thévenod (2018). 15. Iron and Its Role in Cancer Defense: A Double-Edged Sword. In Astrid Sigel, Helmut Sigel, Eva Freisinger, Roland K.O. Sigel (Eds.), Metallo-Drugs: Development and Action of Anticancer Agents (pp. 437–468). Berlin, Boston: De Gruyter. https://doi.org/10.1515/9783110470734-021

Book DOI: https://doi.org/10.1515/9783110470734

Online ISBN: 9783110470734

© 2018 Walter de Gruyter GmbH, Berlin/Munich/BostonGet Permission

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