Inhibition of Na+/K+-ATPase and cytotoxicity of a few selected gold(III) complexes
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Petrović, VoinPetrović, Sandra
Joksić, Gordana
Savić, Jasmina
Čolović, Mirjana B.
Cinellu, Maria Agostina
Massai, Lara
Messori, Luigi
Vasić, Vesna M.
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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. (C) ...2014 Elsevier Inc. All rights reserved.
Keywords:
Sodium pump / Gold(III) complexes / Human blood cells / Inhibition / CytotoxicitySource:
Journal of Inorganic Biochemistry, 2014, 140, 228-235Funding / projects:
- Studies of enzyme interactions with toxic and pharmacologically active molecules (RS-MESTD-Basic Research (BR or ON)-172023)
- AIRC [IG-12085], Beneficentia Stiftung Vaduz
DOI: 10.1016/j.jinorgbio.2014.07.015
ISSN: 0162-0134; 1873-3344
PubMed: 25173578
WoS: 000342608900028
Scopus: 2-s2.0-84906965293
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VinčaTY - JOUR AU - Petrović, Voin AU - Petrović, Sandra AU - Joksić, Gordana AU - Savić, Jasmina AU - Čolović, Mirjana B. AU - Cinellu, Maria Agostina AU - Massai, Lara AU - Messori, Luigi AU - Vasić, Vesna M. PY - 2014 UR - https://vinar.vin.bg.ac.rs/handle/123456789/140 AB - 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. (C) 2014 Elsevier Inc. All rights reserved. T2 - Journal of Inorganic Biochemistry T1 - Inhibition of Na+/K+-ATPase and cytotoxicity of a few selected gold(III) complexes VL - 140 SP - 228 EP - 235 DO - 10.1016/j.jinorgbio.2014.07.015 ER -
@article{ author = "Petrović, Voin and Petrović, Sandra and Joksić, Gordana and Savić, Jasmina and Čolović, Mirjana B. and Cinellu, Maria Agostina and Massai, Lara and Messori, Luigi and Vasić, Vesna M.", year = "2014", 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. (C) 2014 Elsevier Inc. All rights reserved.", journal = "Journal of Inorganic Biochemistry", title = "Inhibition of Na+/K+-ATPase and cytotoxicity of a few selected gold(III) complexes", volume = "140", pages = "228-235", doi = "10.1016/j.jinorgbio.2014.07.015" }
Petrović, V., Petrović, S., Joksić, G., Savić, J., Čolović, M. B., Cinellu, M. A., Massai, L., Messori, L.,& Vasić, V. M.. (2014). Inhibition of Na+/K+-ATPase and cytotoxicity of a few selected gold(III) complexes. in Journal of Inorganic Biochemistry, 140, 228-235. https://doi.org/10.1016/j.jinorgbio.2014.07.015
Petrović V, Petrović S, Joksić G, Savić J, Čolović MB, Cinellu MA, Massai L, Messori L, Vasić VM. Inhibition of Na+/K+-ATPase and cytotoxicity of a few selected gold(III) complexes. in Journal of Inorganic Biochemistry. 2014;140:228-235. doi:10.1016/j.jinorgbio.2014.07.015 .
Petrović, Voin, Petrović, Sandra, Joksić, Gordana, Savić, Jasmina, Čolović, Mirjana B., Cinellu, Maria Agostina, Massai, Lara, Messori, Luigi, Vasić, Vesna M., "Inhibition of Na+/K+-ATPase and cytotoxicity of a few selected gold(III) complexes" in Journal of Inorganic Biochemistry, 140 (2014):228-235, https://doi.org/10.1016/j.jinorgbio.2014.07.015 . .