期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1863, 期 8, 页码 2044-2053出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamcr.2016.04.027
关键词
Gallium; Iron; Metallodrug therapeutics; Cancer; Infection; Ribonucleotide reductase
资金
- Thomas A. and Lorraine M. Rosenberg Award for Translational Cancer Research from Froedtert Hospital Foundation
- Medical College of Wisconsin
Gallium, a group Illa metal, shares chemical properties with iron. Studies have shown that gallium-based compounds have potential therapeutic activity against certain cancers and infectious microorganisms. By functioning as an iron mimetic, gallium perturbs iron-dependent proliferation processes in tumor cells. Gallium's action on iron homeostasis leads to disruption of ribonucleotide reductase, mitochondrial function, and the regulation of transferrin receptor and ferritin. In addition, gallium nitrate stimulates an increase in mitochondrial reactive oxygen species in cells which triggers downstream upregulation of metailothionein and hemoxygenase-1. Gallium's anti-infective activity against bacteria and fungi results from disruption of microbial iron utilization through mechanisms which include gallium binding to siderophores and downregulation of bacterial iron uptake. Gallium compounds lack cross-resistance to conventional chemotherapeutic drugs and antibiotics thus making them attractive agents for drug development. This review will focus on the mechanisms of action of gallium with emphasis on its interaction with iron and iron proteins. (C) 2016 Elsevier B.V. All rights reserved.
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