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Studies on the binding affinity of anticancer drug mitoxantrone to chromatin, DNA and histone proteins

Mitoxantrone is a potent antitumor drug, widely used in the treatment of various cancers. In the present study, we have investigated and compared the affinity of anticancer drug, mitoxantrone, to EDTA-soluble chromatin (SE-chromatin), DNA and histones employing UV/Vis, fluorescence, CD spectroscopy,...

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Autores principales: Hajihassan, Zahra, Rabbani-Chadegani, Azra
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2660295/
https://www.ncbi.nlm.nih.gov/pubmed/19284573
http://dx.doi.org/10.1186/1423-0127-16-31
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author Hajihassan, Zahra
Rabbani-Chadegani, Azra
author_facet Hajihassan, Zahra
Rabbani-Chadegani, Azra
author_sort Hajihassan, Zahra
collection PubMed
description Mitoxantrone is a potent antitumor drug, widely used in the treatment of various cancers. In the present study, we have investigated and compared the affinity of anticancer drug, mitoxantrone, to EDTA-soluble chromatin (SE-chromatin), DNA and histones employing UV/Vis, fluorescence, CD spectroscopy, gel electrophoresis and equilibrium dialysis techniques. The results showed that the interaction of mitoxantrone with SE-chromatin proceeds into compaction/aggregation as revealed by reduction in the absorbencies at 608 and 260 nm (hypochromicity) and disappearance of both histones and DNA on the gels. Mitoxantrone interacts strongly with histone proteins in solution making structural changes in the molecule as shown by CD and fluorescence analysis. The binding isotherms demonstrate a positive cooperative binding pattern for the chromatin- mitoxantrone interaction. It is suggested higher binding affinity of mitoxantrone to chromatin compared to DNA implying that the histone proteins may play an important role in the chromatin- mitoxantrone interaction process.
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spelling pubmed-26602952009-03-25 Studies on the binding affinity of anticancer drug mitoxantrone to chromatin, DNA and histone proteins Hajihassan, Zahra Rabbani-Chadegani, Azra J Biomed Sci Research Mitoxantrone is a potent antitumor drug, widely used in the treatment of various cancers. In the present study, we have investigated and compared the affinity of anticancer drug, mitoxantrone, to EDTA-soluble chromatin (SE-chromatin), DNA and histones employing UV/Vis, fluorescence, CD spectroscopy, gel electrophoresis and equilibrium dialysis techniques. The results showed that the interaction of mitoxantrone with SE-chromatin proceeds into compaction/aggregation as revealed by reduction in the absorbencies at 608 and 260 nm (hypochromicity) and disappearance of both histones and DNA on the gels. Mitoxantrone interacts strongly with histone proteins in solution making structural changes in the molecule as shown by CD and fluorescence analysis. The binding isotherms demonstrate a positive cooperative binding pattern for the chromatin- mitoxantrone interaction. It is suggested higher binding affinity of mitoxantrone to chromatin compared to DNA implying that the histone proteins may play an important role in the chromatin- mitoxantrone interaction process. BioMed Central 2009-03-11 /pmc/articles/PMC2660295/ /pubmed/19284573 http://dx.doi.org/10.1186/1423-0127-16-31 Text en Copyright © 2009 Hajihassan and Rabbani-Chadegani; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Hajihassan, Zahra
Rabbani-Chadegani, Azra
Studies on the binding affinity of anticancer drug mitoxantrone to chromatin, DNA and histone proteins
title Studies on the binding affinity of anticancer drug mitoxantrone to chromatin, DNA and histone proteins
title_full Studies on the binding affinity of anticancer drug mitoxantrone to chromatin, DNA and histone proteins
title_fullStr Studies on the binding affinity of anticancer drug mitoxantrone to chromatin, DNA and histone proteins
title_full_unstemmed Studies on the binding affinity of anticancer drug mitoxantrone to chromatin, DNA and histone proteins
title_short Studies on the binding affinity of anticancer drug mitoxantrone to chromatin, DNA and histone proteins
title_sort studies on the binding affinity of anticancer drug mitoxantrone to chromatin, dna and histone proteins
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2660295/
https://www.ncbi.nlm.nih.gov/pubmed/19284573
http://dx.doi.org/10.1186/1423-0127-16-31
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