title: 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.
authors.affiliation: Department of Physical Chemistry, Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia.
authors.forename: Voin
authors.initials: V
authors.lastname: Petrović
authors.affiliation: Department of Physical Chemistry, Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Petrović
authors.affiliation: Department of Physical Chemistry, Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia.
authors.forename: Gordana
authors.initials: G
authors.lastname: Joksić
authors.affiliation: Department of Physical Chemistry, Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Savić
authors.affiliation: Department of Physical Chemistry, Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Čolović
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, Via Vienna 2, 07100 Sassari, Italy.
authors.forename: Maria Agostina
authors.initials: MA
authors.lastname: Cinellu
authors.affiliation: Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy.
authors.forename: Lara
authors.initials: L
authors.lastname: Massai
authors.affiliation: Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Messori
authors.affiliation: Department of Physical Chemistry, Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia. Electronic address: evasic@vin.bg.ac.rs.
authors.forename: Vesna
authors.initials: V
authors.lastname: Vasić
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D006046:Gold / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D015162:Micronucleus Tests; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000970:Antineoplastic Agents; D006046:Gold; D000254:Sodium-Potassium-Exchanging ATPase
keywords: Cytotoxicity; Gold(III) complexes; Human blood cells; Inhibition; Sodium pump