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Summary
August 2007, Vol. 11, No. 8, Pages 1043-1053
, DOI 10.1517/14728222.11.8.1043
Digitoxin as an anticancer agent with selectivity for cancer cells: possible mechanisms involvedMiguel López-LázaroAssociate Professor University of Seville, Department of Pharmacology, Faculty of Pharmacy, C/Profesor Garcia Gonzalez, 41012, Sevilla, Spain +34 954 55 61 24; +34 954 23 37 65; mlopezlazaro@us.es Accumulating preclinical and clinical data suggest that the cardiac drug digitoxin might be used in cancer therapy. Recent reports have shown that digitoxin can inhibit the growth and induce apoptosis in cancer cells at concentrations commonly found in the plasma of cardiac patients treated with this drug. Several mechanisms have been associated with the anticancer activity of digitoxin, yet at present it is unknown why malignant cells are more susceptible to this cardiac glycoside than non-malignant cells. This report analyses the possible anticancer mechanisms of digitoxin and proposes that the inhibition of glycolysis may be a key mechanism by which this natural product selectively targets cancer cells. Finally, whether or not there is enough evidence to support the clinical evaluation of digitoxin in patients with cancer is discussed. Forward Links to Citing ArticlesVladimir Gogvadze, Sten Orrenius, Boris Zhivotovsky. (2009) Mitochondria as targets for chemotherapy. Apoptosis 14:4, 624-640 Online publication date: 1-May-2009. CrossRef M. Lopez-Lazaro. (2009) Digoxin, HIF-1, and cancer. Proceedings of the National Academy of Sciences 106:9, E26-E26 Online publication date: 13-Mar-2009. CrossRef Elena Bloise, Alessandra Braca, Nunziatina Tommasi, Maria Antonietta Belisario. (2009) Pro-apoptotic and cytostatic activity of naturally occurring cardenolides. Cancer Chemotherapy and Pharmacology Online publication date: 28-Feb-2009. CrossRef Raj K. Koiri, Surendra K. Trigun, Lallan Mishra, Kiran Pandey, Deobrat Dixit, Santosh K. Dubey. (2008) Regression of Dalton’s lymphoma in vivo via decline in lactate dehydrogenase and induction of apoptosis by a ruthenium(II)-complex containing 4-carboxy N-ethylbenzamide as ligand. Investigational New Drugs Online publication date: 29-Dec-2008. CrossRef Ioannis Prassas, Eleftherios P. Diamandis. (2008) Novel therapeutic applications of cardiac glycosides. Nature Reviews Drug Discovery 7:11, 926-935 Online publication date: 1-Dec-2008. CrossRef Tatjana Mijatovic, Laurent Ingrassia, Vincenzo Facchini, Robert Kiss. (2008) Na+/K+-ATPase α subunits as new targets in anticancer therapy. Expert Opinion on Therapeutic Targets 12:11, 1403-1417 Online publication date: 1-Nov-2008. Summary | Full Text | PDF (380 KB) | PDF Plus (347 KB) |
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