In vitro effects of some gold complexes on Na+/K+ ATPase activity and cell proliferation
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Petrovic, VoinČolović, Mirjana B.
Krstić, Danijela Z.
Vujačić, Ana V.
Petrović, Sandra
Joksić, Gordana
Bugarčić, Živadin D.
Vasić, Vesna M.
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The in vitro influence of gold(III) complexes, H[AuCl4], [Au(DMSO)(2)Cl-2]Cl and [Au(bipy)Cl-2]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 x 10(-7), 5.50 x 10(-6) and 3.98 x 10(-5), for H[AuCl4], [Au(DMSO)(2)Cl-2]Cl and [Au(bipy)Cl-2]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 redu...cing maximum enzymatic velocity, V-max, but not significantly changing the affinity for the substrate (K-M value), implying a noncompetitive mode of the interaction. Furthermore, among investigated gold(III) complexes, the [Au(bipy)Cl-2]Cl complex exhibits a strong cytotoxic effect on human lymphocytes, which suggests its potential for use in antitumor therapy. (C(C) 2013 Elsevier Inc. All rights reserved.
Keywords:
Gold(III) complexes / Na+/K+ ATPase / Inhibition / Prevention / Recovery / Cell proliferationSource:
Journal of Inorganic Biochemistry, 2013, 124, 35-41Funding / projects:
- Studies of enzyme interactions with toxic and pharmacologically active molecules (RS-MESTD-Basic Research (BR or ON)-172023)
DOI: 10.1016/j.jinorgbio.2013.03.013
ISSN: 0162-0134
PubMed: 23591145
WoS: 000320087100005
Scopus: 2-s2.0-84875992731
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VinčaTY - JOUR AU - Petrovic, Voin AU - Čolović, Mirjana B. AU - Krstić, Danijela Z. AU - Vujačić, Ana V. AU - Petrović, Sandra AU - Joksić, Gordana AU - Bugarčić, Živadin D. AU - Vasić, Vesna M. PY - 2013 UR - https://vinar.vin.bg.ac.rs/handle/123456789/5539 AB - The in vitro influence of gold(III) complexes, H[AuCl4], [Au(DMSO)(2)Cl-2]Cl and [Au(bipy)Cl-2]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 x 10(-7), 5.50 x 10(-6) and 3.98 x 10(-5), for H[AuCl4], [Au(DMSO)(2)Cl-2]Cl and [Au(bipy)Cl-2]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, V-max, but not significantly changing the affinity for the substrate (K-M value), implying a noncompetitive mode of the interaction. Furthermore, among investigated gold(III) complexes, the [Au(bipy)Cl-2]Cl complex exhibits a strong cytotoxic effect on human lymphocytes, which suggests its potential for use in antitumor therapy. (C(C) 2013 Elsevier Inc. All rights reserved. T2 - Journal of Inorganic Biochemistry T1 - In vitro effects of some gold complexes on Na+/K+ ATPase activity and cell proliferation VL - 124 SP - 35 EP - 41 DO - 10.1016/j.jinorgbio.2013.03.013 ER -
@article{ author = "Petrovic, Voin and Čolović, Mirjana B. and Krstić, Danijela Z. and Vujačić, Ana V. and Petrović, Sandra and Joksić, Gordana and Bugarčić, Živadin D. and Vasić, Vesna M.", year = "2013", abstract = "The in vitro influence of gold(III) complexes, H[AuCl4], [Au(DMSO)(2)Cl-2]Cl and [Au(bipy)Cl-2]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 x 10(-7), 5.50 x 10(-6) and 3.98 x 10(-5), for H[AuCl4], [Au(DMSO)(2)Cl-2]Cl and [Au(bipy)Cl-2]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, V-max, but not significantly changing the affinity for the substrate (K-M value), implying a noncompetitive mode of the interaction. Furthermore, among investigated gold(III) complexes, the [Au(bipy)Cl-2]Cl complex exhibits a strong cytotoxic effect on human lymphocytes, which suggests its potential for use in antitumor therapy. (C(C) 2013 Elsevier Inc. All rights reserved.", journal = "Journal of Inorganic Biochemistry", title = "In vitro effects of some gold complexes on Na+/K+ ATPase activity and cell proliferation", volume = "124", pages = "35-41", doi = "10.1016/j.jinorgbio.2013.03.013" }
Petrovic, V., Čolović, M. B., Krstić, D. Z., Vujačić, A. V., Petrović, S., Joksić, G., Bugarčić, Ž. D.,& Vasić, V. M.. (2013). In vitro effects of some gold complexes on Na+/K+ ATPase activity and cell proliferation. in Journal of Inorganic Biochemistry, 124, 35-41. https://doi.org/10.1016/j.jinorgbio.2013.03.013
Petrovic V, Čolović MB, Krstić DZ, Vujačić AV, Petrović S, Joksić G, Bugarčić ŽD, Vasić VM. In vitro effects of some gold complexes on Na+/K+ ATPase activity and cell proliferation. in Journal of Inorganic Biochemistry. 2013;124:35-41. doi:10.1016/j.jinorgbio.2013.03.013 .
Petrovic, Voin, Čolović, Mirjana B., Krstić, Danijela Z., Vujačić, Ana V., Petrović, Sandra, Joksić, Gordana, Bugarčić, Živadin D., Vasić, Vesna M., "In vitro effects of some gold complexes on Na+/K+ ATPase activity and cell proliferation" in Journal of Inorganic Biochemistry, 124 (2013):35-41, https://doi.org/10.1016/j.jinorgbio.2013.03.013 . .