Inhibition of Na(+)/K(+)-ATPase and cytotoxicity of a few selected gold(III) complexes

Abstract

Na(+)/K(+)-ATPase is in charge of maintaining the ionic and osmotic intracellular balance by using ATP as an energy source to drive excess Na(+) ions out of the cell in exchange for K(+) ions. We explored whether three representative cytotoxic gold(III) compounds might interfere with Na(+)/K(+)-ATPase and cause its inhibition at pharmacologically relevant concentrations. The tested complexes were [Au(bipy)(OH)2][PF6] (bipy=2,2'-bipyridine), [Au(py(dmb)-H)(CH3COO)2] (py(dmb)-H=deprotonated 6-(1,1-dimethylbenzyl)-pyridine), and [Au(bipy(dmb)-H)(OH)][PF6] (bipy(dmb)-H=deprotonated 6-(1,1-dimethylbenzyl)-2,2'-bipyridine). We found that all of them caused a pronounced and similar inhibition of Na(+)/K(+)-ATPase activity. Inhibition was found to be non-competitive and reversible. Remarkably, treatment with cysteine resulted in reversal or prevention of Na(+)/K(+)-ATPase inhibition. It is very likely that the described effects may contribute to the overall cytotoxic profile of these gold complexes.

Keywords: Cytotoxicity; Gold(III) complexes; Human blood cells; Inhibition; Sodium pump.