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

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Hajihassan Z, Rabbani-Chadegani A

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

J Biomed Sci. 2009 Mar 11;16:31. doi: 10.1186/1423-0127-16-31.

PubMed ID

19284573 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Mitoxantrone	DNA	Nucleotide	Humans	Yes	Intercalation	Details