Gallium and its competing roles with iron in biological systems. Biochim Biophys Acta 2016 Aug;1863(8):2044-53
Date
05/08/2016Pubmed ID
27150508DOI
10.1016/j.bbamcr.2016.04.027Scopus ID
2-s2.0-84971367758 (requires institutional sign-in at Scopus site) 217 CitationsAbstract
Gallium, a group IIIa 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 metallothionein 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.
Author List
Chitambar CRMESH terms used to index this publication - Major topics in bold
AnimalsAnti-Infective Agents
Antineoplastic Agents
Biological Transport
Drug Evaluation
Drug Screening Assays, Antitumor
Gallium
Gallium Isotopes
Homeostasis
Humans
Iron
Mice
Mitochondria
Neoplasms
Nonheme Iron Proteins
Rats
Transferrin
