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Cytotoxicity of digitoxin and related cardiac glycosides in human tumor cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Pharmacognosy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Pharmacognosy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Cancer Pharmacology and Informatics)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Cancer Pharmacology and Informatics)
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2001 (English)In: Anti-Cancer Drugs, ISSN 0959-4973, E-ISSN 1473-5741, Vol. 12, no 5, 475-83 p.Article in journal (Refereed) Published
Abstract [en]

The saponin digitonin, the aglycone digitoxigenin and five cardiac glycosides were evaluated for cytotoxicity using primary cultures of tumor cells from patients and a human cell line panel (representing different cytotoxic drug-resistance patterns). Of these seven compounds, proscillaridin A was the most potent (IC(50): 6.4--76 nM), followed by digitoxin, and then ouabain, digoxin, lanatoside C, digitoxigenin and digitonin. Correlation analysis of the log IC(50) values for the cell lines in the panel showed that compound cytotoxicity was only slightly influenced by resistance mechanisms that involved P-glycoprotein, topoisomerase II, multidrug resistance-associated protein and glutathione-mediated drug resistance. Digitoxin and digoxin expressed selective toxicity against solid tumor cells from patients, while proscillaridin A expressed no selective toxicity against either solid or hematological tumor cells. The results revealed marked differences in cytotoxicity between the cardiac glycosides, both in potency and selectivity, and modes of action for cytotoxicity that differ from that of commonly used anticancer drugs.

Place, publisher, year, edition, pages
2001. Vol. 12, no 5, 475-83 p.
Keyword [en]
Cytotoxicity drug screening, digitalis glycosides, digitonin, digitoxigenin, digitoxin, digoxin, lanatoside C, ouabain, proscillaridin A, tumor cell lines
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-51277PubMedID: 11395576OAI: oai:DiVA.org:uu-51277DiVA: diva2:79186
Available from: 2007-02-08 Created: 2007-02-08 Last updated: 2017-12-04Bibliographically approved

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Gullbo, JoachimLarsson, Rolf

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