Cytotoxic Effects of Cardiac Glycosides in Colon Cancer Cells, Alone and in Combination with Standard Chemotherapeutic Drugs. Journal of natural products [J Nat Prod] Journal article | | Title | Cytotoxic Effects of Cardiac Glycosides in Colon Cancer Cells, Alone and in Combination with Standard Chemotherapeutic Drugs. | | Author(s) | Felth J, Rickardson L, Rosén J, Wickström M, Fryknäs M, Lindskog M, Bohlin L, Gullbo J | | Institution | Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Center, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden, and Division of Clinical Pharmacology, Department of Medical Sciences, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. | | Source | J Nat Prod 2009 Nov 6. | | Abstract | Cardiac glycosides have been reported to exhibit cytotoxic activity against several different cancer types, but studies against colorectal cancer are lacking. In a screening procedure aimed at identifying natural products with activity against colon cancer, several cardiac glycosides were shown to be of interest, and five of these were further evaluated in different colorectal cancer cell lines and primary cells from patients. Convallatoxin (1), oleandrin (4), and proscillaridin A (5) were identified as the most potent compounds (submicromolar IC(50) values), and digitoxin (2) and digoxin (3), which are used in cardiac disease, exhibited somewhat lower activity (IC(50) values 0.27-4.1 muM). Selected cardiac glycosides were tested in combination with four clinically relevant cytotoxic drugs (5-fluorouracil, oxaliplatin, cisplatin, irinotecan). The combination of 2 and oxaliplatin exhibited synergism including the otherwise highly drug-resistant HT29 cell line. A ChemGPS-NP application comparing modes of action of anticancer drugs identified cardiac glycosides as a separate cluster. These findings demonstrate that such substances may exhibit significant activity against colorectal cancer cell lines, by mechanisms disparate from currently used anticancer drugs, but at concentrations generally considered not achievable in patient plasma. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19894733 |
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