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Effects of Hypoxia and Transferrin on Toxicity and DNA Binding of Ruthenium Antitumor Agents in Hela Cells

Nuclear DNA binding and inhibition of growth of HeLa cells in culture were determined after 24 h incubation with the ruthenium anticancer agents cis-[Cl(2)(NH(3))(4)Ru]Cl (CCR) and (ImH)trans-[(Im)(2)Cl(4)Ru] (ICR) as a function of [Ru], Po(2), and added transferrin. Consistent with the “activation-...

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Detalles Bibliográficos
Autores principales: Frasca, D., Ciampa, J., Emerson, J., Umans, R. S., Clarke, M. J.
Formato: Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 1996
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2365025/
https://www.ncbi.nlm.nih.gov/pubmed/18475755
http://dx.doi.org/10.1155/MBD.1996.197
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author Frasca, D.
Ciampa, J.
Emerson, J.
Umans, R. S.
Clarke, M. J.
author_facet Frasca, D.
Ciampa, J.
Emerson, J.
Umans, R. S.
Clarke, M. J.
author_sort Frasca, D.
collection PubMed
description Nuclear DNA binding and inhibition of growth of HeLa cells in culture were determined after 24 h incubation with the ruthenium anticancer agents cis-[Cl(2)(NH(3))(4)Ru]Cl (CCR) and (ImH)trans-[(Im)(2)Cl(4)Ru] (ICR) as a function of [Ru], Po(2), and added transferrin. Consistent with the “activation-by-reduction” hypothesis, cytotoxicity and DNA binding for both complexes increased under reduced oxygen conditions. Consistent with the “transferrin- transport” hypothesis, inhibition of cell growth also increased with added transferrin for both complexes. Despite their differences in charge, reduction potentials and substitution rates, both complexes behaved remarkably similarly indicating a common mechanism of action for both. Under atmospheric Conditions (Po(2) = 159 torr), CCR inhibited HeLa cell growth with IC(50) = 3.5 μM, while that for ICR was 2.0 μM. The binding of both complexes to DNA (Ru(DNA)/P(DNA)) correlated with toxicity and was approximately linear in the concentration of the ruthenium complex in the culture medium, [Ru]. For both complexes, IC(50) values decrease and DNA binding increases with decreasing log(Po(2)). In general, DNA binding at all oxygen pressures for both complexes is in the range of one Ru per 1000-2000 DNA base pairs at [Ru] = IC(50).
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spelling pubmed-23650252008-05-12 Effects of Hypoxia and Transferrin on Toxicity and DNA Binding of Ruthenium Antitumor Agents in Hela Cells Frasca, D. Ciampa, J. Emerson, J. Umans, R. S. Clarke, M. J. Met Based Drugs Research Article Nuclear DNA binding and inhibition of growth of HeLa cells in culture were determined after 24 h incubation with the ruthenium anticancer agents cis-[Cl(2)(NH(3))(4)Ru]Cl (CCR) and (ImH)trans-[(Im)(2)Cl(4)Ru] (ICR) as a function of [Ru], Po(2), and added transferrin. Consistent with the “activation-by-reduction” hypothesis, cytotoxicity and DNA binding for both complexes increased under reduced oxygen conditions. Consistent with the “transferrin- transport” hypothesis, inhibition of cell growth also increased with added transferrin for both complexes. Despite their differences in charge, reduction potentials and substitution rates, both complexes behaved remarkably similarly indicating a common mechanism of action for both. Under atmospheric Conditions (Po(2) = 159 torr), CCR inhibited HeLa cell growth with IC(50) = 3.5 μM, while that for ICR was 2.0 μM. The binding of both complexes to DNA (Ru(DNA)/P(DNA)) correlated with toxicity and was approximately linear in the concentration of the ruthenium complex in the culture medium, [Ru]. For both complexes, IC(50) values decrease and DNA binding increases with decreasing log(Po(2)). In general, DNA binding at all oxygen pressures for both complexes is in the range of one Ru per 1000-2000 DNA base pairs at [Ru] = IC(50). Hindawi Publishing Corporation 1996 /pmc/articles/PMC2365025/ /pubmed/18475755 http://dx.doi.org/10.1155/MBD.1996.197 Text en Copyright © 1996 Hindawi Publishing Corporation. http://creativecommons.org/licenses/by/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Frasca, D.
Ciampa, J.
Emerson, J.
Umans, R. S.
Clarke, M. J.
Effects of Hypoxia and Transferrin on Toxicity and DNA Binding of Ruthenium Antitumor Agents in Hela Cells
title Effects of Hypoxia and Transferrin on Toxicity and DNA Binding of Ruthenium Antitumor Agents in Hela Cells
title_full Effects of Hypoxia and Transferrin on Toxicity and DNA Binding of Ruthenium Antitumor Agents in Hela Cells
title_fullStr Effects of Hypoxia and Transferrin on Toxicity and DNA Binding of Ruthenium Antitumor Agents in Hela Cells
title_full_unstemmed Effects of Hypoxia and Transferrin on Toxicity and DNA Binding of Ruthenium Antitumor Agents in Hela Cells
title_short Effects of Hypoxia and Transferrin on Toxicity and DNA Binding of Ruthenium Antitumor Agents in Hela Cells
title_sort effects of hypoxia and transferrin on toxicity and dna binding of ruthenium antitumor agents in hela cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2365025/
https://www.ncbi.nlm.nih.gov/pubmed/18475755
http://dx.doi.org/10.1155/MBD.1996.197
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