Competition between abiogenic and biogenic metal cations in biological systems: Mechanisms of gallium's anticancer and antibacterial effect

Metal cations are key players in a plethora of essential biological processes. Over the course of evolution specific biological functions have been bestowed upon two dozen of (biogenic) metal species, some of the most frequently found being sodium, potassium, magnesium, calcium, zinc, manganese, iron, and copper. On the other hand, there is a group of less studied abiogenic metals like lithium, strontium and gallium that possess not known functions in living organisms, but, by mimicking the native ions and/or competing with them for binding to key metalloenzymes, may exert beneficial effect on humans in particular medical conditions. This review summarizes and critically examines the mechanisms of gallium's therapeutic action in anticancer and antibacterial therapies by exploiting the tools of molecular modeling and experimental biochemistry. These approaches allow for identifying key factors for Ga3+ beneficial effect such as the electrostatic interactions with the protein ligands, substrates or bacterial siderophores, intramolecular hydrogen bond formation, and pH and dielectric properties of the medium. Several intriguing questions concerning the gallium competition with the native ferric ion have found their answers.

Automated summary

Metal cations play crucial roles in biological processes, with some biogenic metals like sodium, potassium, magnesium, and calcium being commonly found and possessing specific functions. Abiogenic metals such as lithium, strontium, and gallium, which mimic native ions or compete with them for binding to key metalloenzymes, may have beneficial effects on humans in certain medical conditions. This review critically examines the therapeutic mechanisms of gallium in anticancer and antibacterial therapies through molecular modeling and experimental biochemistry, identifying factors like electrostatic interactions and pH that contribute to Ga3+'s beneficial effects.