Faculty Collaboration Database

The therapeutic potential of iron-targeting gallium compounds in human disease: From basic research to clinical application. Pharmacol Res 2017 Jan;115:56-64

Date

11/20/2016

Pubmed ID

27856328

DOI

10.1016/j.phrs.2016.11.009

Scopus ID

2-s2.0-84995688314 (requires institutional sign-in at Scopus site)   84 Citations

Abstract

Gallium, group IIIa metal, shares certain chemical characteristics with iron which enable it to function as an iron mimetic that can disrupt iron-dependent tumor cell growth. Gallium may also display antimicrobial activity by disrupting iron homeostasis in certain bacteria and fungi. Gallium's action on iron homeostasis leads to inhibition of ribonucleotide reductase, mitochondrial function, and changes in proteins of iron transport and storage. In addition, gallium induces an increase in mitochondrial reactive oxygen species in cells which triggers downstream upregulation of metallothionein and hemoxygenase-1. Early clinical trials evaluated the efficacy of the simple gallium salts, gallium nitrate and gallium chloride. However, newer gallium-ligands such as Tris(8-quinolinolato)gallium(III) (KP46) and gallium maltolate have been developed and are undergoing clinical evaluation. Additional gallium-ligands that demonstrate antitumor activity in preclinical studies have emerged. Their mechanisms of action and their spectrum of antitumor activity may extend beyond the earlier generations of gallium compounds and warrant further investigation. This review will focus on the evolution and potential of gallium-based therapeutics.

Author List

Chitambar CR

MESH terms used to index this publication - Major topics in bold

Animals
Antineoplastic Agents
Gallium
Humans
Iron
Ligands
Mitochondria