Abstract
BackgroundDigitoxin induces apoptosis in different human malignant cell lines in vitro. In this paper we investigated if patients taking digitoxin for cardiac disease have a different cancer incidence compared to the general population.MethodsComputer stored data on digitoxin concentrations in plasma from 9271 patients with cardiac disease were used to define a user population. Age and sex matched controls from the Norwegian Cancer Registry were used to calculate the number of expected cancer cases.ResultsThe population on digitoxin showed a higher incidence of cancer compared to the control population. However, an additional analysis showed that the population on digitoxin had a general increased risk of cancer already, before the start on digitoxin. Leukemia/lymphoma were the cancer types which stood out with the highest risk in the digitoxin population before starting on digitoxin. This indicates that yet unknown risk factors exist for cardiovascular disease and lymphoproliferative cancer.An internal dose-response analysis revealed a relationship between high plasma concentration of digitoxin and a lower risk for leukemia/lymphoma and for cancer of the kidney/urinary tract.ConclusionMorbidity and mortality are high in the population on digitoxin, due to high age and cardiac disease.These factors disturb efforts to isolate an eventual anticancer effect of digitoxin in this setting. Still, the results may indicate an anticancer effect of digitoxin for leukemia/lymphoma and kidney/urinary tract cancers. Prospective clinical cancer trials have to be done to find out if digitoxin and other cardiac glycosides are useful as anticancer agents.
Highlights
Digitoxin induces apoptosis in different human malignant cell lines in vitro
Morbidity and mortality are high in the population on digitoxin, due to high age and cardiac disease.These factors disturb efforts to isolate an eventual anticancer effect of digitoxin in this setting
Prospective clinical cancer trials have to be done to find out if digitoxin and other cardiac glycosides are useful as anticancer agents
Summary
Digitoxin induces apoptosis in different human malignant cell lines in vitro. In this paper we investigated if patients taking digitoxin for cardiac disease have a different cancer incidence compared to the general population. Some cardiac glycosides have been evaluated in short term animal models. The conclusion from these experiments is that very high doses, probably toxic, would be needed for obtaining anticancer effects in humans [6]. We have previously found that non toxic concentrations of digitoxin and digoxin inhibits growth and induce apoptosis in different human malignant cell lines, whereas highly proliferating normal cells were not affected [7,8,9]. There is a great difference in susceptibility for cardiac glycosides in different species indicating that one can not extrapolate the results from animal models into humans [4]
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