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Cytotoxic effects o...
Cytotoxic effects of cardiac glycosides in colon cancer cells, alone and in combination with standard chemotherapeutic drugs
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- Felth, Jenny (författare)
- Uppsala universitet,Avdelningen för farmakognosi
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- Rickardson, Linda (författare)
- Uppsala universitet,Klinisk farmakologi,Cancer Pharmacology and Informatics/Rolf Larsson
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- Rosén, Josefin (författare)
- Uppsala universitet,Avdelningen för farmakognosi
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- Wickström, Malin (författare)
- Uppsala universitet,Klinisk farmakologi,Cancer Pharmacology and Informatics/Rolf Larsson
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- Fryknäs, Mårten (författare)
- Uppsala universitet,Klinisk farmakologi,Cancer Pharmacology and Informatics/Rolf Larsson
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- Lindskog, Magnus (författare)
- Karolinska Institutet,Uppsala universitet,Klinisk farmakologi
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- Bohlin, Lars (författare)
- Uppsala universitet,Avdelningen för farmakognosi
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- Gullbo, Joachim (författare)
- Uppsala universitet,Klinisk farmakologi,Cancer Pharmacology and Informatics/Rolf Larsson
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(creator_code:org_t)
- 2009-11-06
- 2009
- Engelska.
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Ingår i: Journal of natural products (Print). - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 72:11, s. 1969-1974
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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 IC50 values), and digitoxin (2) and digoxin (3), which are used in cardiac disease, exhibited somewhat lower activity (IC50 values 0.27−4.1 μM). 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- PHARMACY
- FARMACI
- Pharmacognosy
- Farmakognosi
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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