%0 Journal Article
%T Inhibition of Na(+)/K(+)-ATPase and cytotoxicity of a few selected gold(III) complexes.
%A Petrović V
%A Petrović S
%A Joksić G
%A Savić J
%A Čolović M
%A Cinellu MA
%A Massai L
%A Messori L
%A Vasić V
%J J Inorg Biochem
%V 140
%N 0
%D Nov 2014
%M 25173578
%F 4.336
%R 10.1016/j.jinorgbio.2014.07.015
%X 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.