Protein Targets for Anticancer Gold Compounds: Mechanistic Inferences

Chiara      Gabbiani; Luigi      Messori

doi:10.2174/187152011797927607

Abstract

Gold compounds form an interesting class of antiproliferative agents of potential pharmacological use in cancer treatment. Indeed, a number of gold compounds, either gold(III) or gold(I), were recently described and characterised that manifested remarkable cytotoxic properties in vitro against cultured cancer cells; for some of them encouraging in vivo results were also reported toward a few relevant animal models of cancer. The molecular mechanisms through which gold compounds exert their biological effects are still largely unknown and the subject of intense investigations. Recent studies point out that the modes of action of cytotoxic gold compounds are essentially DNA-independent and cisplatin-unrelated, relying -most likely- on gold interactions with a variety of protein targets. Notably, a few cellular proteins playing relevant functional roles were proposed to represent effective targets for cytotoxic gold compounds but these hypotheses need adequate validation. The state of the art of this research area and the perspectives for future studies are herein critically analysed and discussed.

Keywords: Gold compounds, cancer, proteins, metal-protein adducts, phosphine complexes, antiproliferative properties, dithiocarbamate complexes, thiosugar ligand, X-ray diffraction, cytochrome c