In vitro effects of some gold complexes on Na+/K+ ATPase activity and cell proliferation

• H[AuCl4], [Au(DMSO)2Cl2]Cl and [Au(bipy)Cl2]Cl inhibit Na+/K+-ATPase activity.
• Na+/K+-ATPase is the most sensitive toward H[AuCl4].
• -SH donating ligands prevent and reactivate inhibition of Na+/K+-ATPase activity.
• Gold(III) complexes exhibit noncompetitive mode of Na+/K+-ATPase inhibition.
• [Au(bipy)Cl2]Cl exhibits strong cytotoxic effect on cultivated human lymphocytes.

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.

These gold complexes have shown a reversible inhibitory effect upon the porcine Na+/K+ ATPase and cytotoxic effects on human lymphocytes.Figure optionsDownload as PowerPoint slide