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抗癌药物伊达比星和阿霉素对可溶性染色质作用的比较。

A comparison of the effect of anticancer drugs, idarubicin and adriamycin, on soluble chromatin.

作者信息

Zahraei Zohreh, Rabbani-Chadegani Azra

机构信息

Institute of Biochemistry and Biophysics, Department of Biochemistry, University of Tehran, Tehran, Iran.

出版信息

Eur J Pharmacol. 2007 Dec 1;575(1-3):28-33. doi: 10.1016/j.ejphar.2007.07.045. Epub 2007 Jul 31.

Abstract

The biological activity of an anticancer agent is related to its physicochemical interaction with biological receptors. In the present study we have investigated and compared the affinity and mode of action of two potent anticancer drugs, adriamycin and idarubicin on soluble chromatin using ultraviolet/visible and fluorescence spectroscopy, hydroxyapatite (HAP) chromatography and gel electrophoresis techniques. The results show that addition of various concentrations of drugs to chromatin solution individually, reduced both absorbance and fluorescence emission intensity of chromatin and precipitated it in a dose dependent manner, however, the extent of reduction was different for two drugs used. This effect was also observed on the histone gel patterns of the drug treated samples revealing that the chromatin is less affected by idarubicin compared to adriamycin implying higher aggregation of chromatin with the former. As hydroxyapatite chromatograms show, histone H1 represented the highest drug binding activity. The results suggest that although adriamycin and idarubicin are both grouped anthracycline antibiotic anticancer drugs, they differ considerably on their binding affinity to cellular chromatin.

摘要

抗癌药物的生物活性与其与生物受体的物理化学相互作用有关。在本研究中,我们使用紫外/可见光谱和荧光光谱、羟基磷灰石(HAP)色谱法和凝胶电泳技术,研究并比较了两种强效抗癌药物阿霉素和伊达比星对可溶性染色质的亲和力和作用方式。结果表明,分别向染色质溶液中添加不同浓度的药物,会降低染色质的吸光度和荧光发射强度,并以剂量依赖的方式使其沉淀,然而,对于所使用的两种药物,降低程度有所不同。在药物处理样品的组蛋白凝胶图谱上也观察到了这种效应,这表明与阿霉素相比,染色质受伊达比星的影响较小,这意味着染色质与前者的聚集程度更高。正如羟基磷灰石色谱图所示,组蛋白H1表现出最高的药物结合活性。结果表明,尽管阿霉素和伊达比星都属于蒽环类抗生素抗癌药物,但它们对细胞染色质的结合亲和力有很大差异。

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