Ex Vivo Activity of Cardiac Glycosides in Acute Leukaemia

Hallböök, Helene (author): Uppsala universitet,Institutionen för medicinska vetenskaper,Hematologi

Fryknäs, Mårten (author): Uppsala universitet,Klinisk farmakologi,Cancer Pharmacology and Informatics/Rolf Larsson

Larsson, Rolf (author): Uppsala universitet,Klinisk farmakologi,Cancer Pharmacology and Informatics/Rolf Larsson

Gullbo, Joachim (author): Uppsala universitet,Klinisk farmakologi,Cancer Pharmacology and Informatics/Rolf Larsson

(creator_code:org_t)

2011-01-05
2011
English.
In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:1, s. e15718-

Related links:: https://journals.plo...; show more...; https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Abstract Subject headings

Background: Despite years of interest in the anti-cancerous effects of cardiac glycosides (CGs), and numerous studies in vitro and in animals, it has not yet been possible to utilize this potential clinically. Reports have demonstrated promising in vitro effects on different targets as well as a possible therapeutic index/selectivity in vitro and in experimental animals. Recently, however, general inhibition of protein synthesis was suggested as the main mechanism of the anti-cancerous effects of CGs. In addition, evidence of species differences of a magnitude sufficient to explain the results of many studies called for reconsideration of earlier results. Principal Findings: In this report we identified primary B-precursor and T-ALL cells as being particularly susceptible to the cytotoxic effects of CGs. Digitoxin appeared most potent and IC50 values for several patient samples were at concentrations that may be achieved in the clinic. Significant protein synthesis inhibition at concentrations corresponding to IC50 was demonstrated in colorectal tumour cell lines moderately resistant to the cytotoxic effects of digoxin and digitoxin, but not in highly sensitive leukaemia cell lines. Conclusion: It is suggested that further investigation regarding CGs may be focused on diagnoses like T-and B-precursor ALL.

By the author/editor: Hallböök, Helene; Felth, Jenny; Eriksson, Anna; Fryknäs, Mårten; Bohlin, Lars; Larsson, Rolf; show more...; Gullbo, Joachim; show less...

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