Inhibition of DNA Topoisomerases 1 and 2, and Growth Inhibition of Breast Cancer MCF-7 Cells by Ouabain, Digoxin and Proscillaridin A
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- Bielawski Krzysztof
- Department of Medicinal Chemistry and Drug Technology, Medical University of Białystok
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- Winnicka Katarzyna
- Department of Pharmaceutical Technology, Medical University of Białystok
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- Bielawska Anna
- Department of Medicinal Chemistry and Drug Technology, Medical University of Białystok
書誌事項
- タイトル別名
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- 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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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 nM), neither agent inhibited topoisomerase I catalytic activity even at concentrations as high as 100 μM. On the other hand, proscillaridin A was a potent poison of topoisomerase I and II activity at nanomolar drug concentrations (30 nM, 100 nM, 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.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 29 (7), 1493-1497, 2006
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204625967104
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- NII論文ID
- 110005602330
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 7960784
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
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- 抄録ライセンスフラグ
- 使用不可