Hajihassan Zahra, Rabbani-Chadegani Azra
Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
J Biomed Sci. 2009 Mar 11;16(1):31. doi: 10.1186/1423-0127-16-31.
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.
米托蒽醌是一种强效抗肿瘤药物，广泛用于治疗各种癌症。在本研究中，我们采用紫外/可见光谱、荧光光谱、圆二色光谱、凝胶电泳和平衡透析技术，研究并比较了抗癌药物米托蒽醌与乙二胺四乙酸可溶性染色质（SE-染色质）、DNA和组蛋白的亲和力。结果表明，米托蒽醌与SE-染色质的相互作用导致染色质压缩/聚集，这表现为608和260nm处吸光度降低（减色效应）以及凝胶上组蛋白和DNA消失。圆二色光谱和荧光分析表明，米托蒽醌在溶液中与组蛋白强烈相互作用，使分子结构发生变化。结合等温线表明染色质与米托蒽醌的相互作用呈现正协同结合模式。这表明米托蒽醌与染色质的结合亲和力高于与DNA的结合亲和力，这意味着组蛋白可能在染色质与米托蒽醌的相互作用过程中发挥重要作用。
