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标题：Inhibition of DNA Topoisomerases I and II, and Growth Inhibition of Breast Cancer MCF-7 Cells by Ouabain, Digoxin and Proscillaridin A
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作者：Krzysztof Bielawski ; Katarzyna Winnicka ; Anna Bielawska 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2006
卷号：29
期号：7
页码：1493-1497
DOI：10.1248/bpb.29.1493
出版社：The Pharmaceutical Society of Japan
摘要：We evaluated the cytotoxicity and underlying mechanisms of cardiac glycosides, including digoxin, ouabain and proscillaridin A, on the proliferation of breast cancer MCF-7 cells. In terms of inhibition of cell proliferation of MCF-7 cells, the compounds rank in the order proscillaridin A>digoxin>ouabain. While both digoxin and ouabain inhibited topoisomerase II catalytic activity at nanomolar concentrations (100 n M ), neither agent inhibited topoisomerase I catalytic activity even at concentrations as high as 100 μ M . On the other hand, proscillaridin A was a potent poison of topoisomerase I and II activity at nanomolar drug concentrations (30 n M , 100 n M , respectively), suggesting that this agent may produce its cytotoxic activity by targeting both enzymes simultaneously. These studies suggest that the stabilization of DNA-topoisomerase II complexes is closely linked to the mechanism of digoxin, ouabain and proscillaridin A cytotoxicity. The potential DNA-binding properties of the cardiac glycosides have been assessed by measuring the displacement of ethidium bromide from calf thymus DNA. These results indicate that digoxin, ouabain and proscillaridin A neither intercalate nor interact with the minor groove of DNA.
关键词：cytotoxicity;digoxin;ouabain;proscillaridin A;breast cancer MCF-7 cell;DNA topoisomerase