title: In vitro effects of some gold complexes on Na(+)/K(+) ATPase activity and cell proliferation.
abstract: The in vitro influence of gold(III) complexes, H[AuCl4], [Au(DMSO)2Cl2]Cl and [Au(bipy)Cl2]Cl (bipy = 2,2'-bipyridine), upon commercially available Na(+)/K(+) ATPase activity, purified from porcine brain cortex, was investigated. Additionally, the complexes were tested on human lymphocytes, and incidence of micronuclei and cell proliferation index was determined. Concentration-dependent inhibition of the enzyme for all three compounds was obtained, but with differing potencies. Calculated IC50 from Hill analysis were (in M): 5.75×10(-7), 5.50×10(-6) and 3.98×10(-5), for H[AuCl4], [Au(DMSO)2Cl2]Cl and [Au(bipy)Cl2]Cl, respectively, while Hill coefficient values, n, were above 1 in all cases. This inhibition can be prevented using -SH donating ligands such as L-Cys and glutathione, and these ligands can also cause a recovery of the enzyme activity after the induced inhibition. Kinetic analysis demonstrated that each of the studied gold(III) complexes affects Na(+)/K(+) ATPase reducing maximum enzymatic velocity, Vmax, but not significantly changing the affinity for the substrate (KM value), implying a noncompetitive mode of the interaction. Furthermore, among investigated gold(III) complexes, the [Au(bipy)Cl2]Cl complex exhibits a strong cytotoxic effect on human lymphocytes, which suggests its potential for use in antitumor therapy.
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.forename: Mirjana
authors.initials: M
authors.lastname: Čolović
authors.forename: Danijela
authors.initials: D
authors.lastname: Krstić
authors.forename: Ana
authors.initials: A
authors.lastname: Vujačić
authors.forename: Sandra
authors.initials: S
authors.lastname: Petrović
authors.forename: Gordana
authors.initials: G
authors.lastname: Joksić
authors.forename: Zivadin
authors.initials: Z
authors.lastname: Bugarčić
authors.forename: Vesna
authors.initials: V
authors.lastname: Vasić
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003603:Cytotoxins / Q000494:pharmacology*; D005260:Female; D017612:Gold Compounds / Q000494:pharmacology*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000201:enzymology*; D008297:Male; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013552:Swine
chemical_list: D003603:Cytotoxins; D017612:Gold Compounds; D000254:Sodium-Potassium-Exchanging ATPase