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Ex Vivo Activity of Cardiac Glycosides in Acute Leukaemia

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 pos...

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Autores principales: Hallböök, Helene, Felth, Jenny, Eriksson, Anna, Fryknäs, Mårten, Bohlin, Lars, Larsson, Rolf, Gullbo, Joachim
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3016342/
https://www.ncbi.nlm.nih.gov/pubmed/21246039
http://dx.doi.org/10.1371/journal.pone.0015718
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author Hallböök, Helene
Felth, Jenny
Eriksson, Anna
Fryknäs, Mårten
Bohlin, Lars
Larsson, Rolf
Gullbo, Joachim
author_facet Hallböök, Helene
Felth, Jenny
Eriksson, Anna
Fryknäs, Mårten
Bohlin, Lars
Larsson, Rolf
Gullbo, Joachim
author_sort Hallböök, Helene
collection PubMed
description 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 IC(50) values for several patient samples were at concentrations that may be achieved in the clinic. Significant protein synthesis inhibition at concentrations corresponding to IC(50) 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.
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spelling pubmed-30163422011-01-18 Ex Vivo Activity of Cardiac Glycosides in Acute Leukaemia Hallböök, Helene Felth, Jenny Eriksson, Anna Fryknäs, Mårten Bohlin, Lars Larsson, Rolf Gullbo, Joachim PLoS One Research Article 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 IC(50) values for several patient samples were at concentrations that may be achieved in the clinic. Significant protein synthesis inhibition at concentrations corresponding to IC(50) 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. Public Library of Science 2011-01-05 /pmc/articles/PMC3016342/ /pubmed/21246039 http://dx.doi.org/10.1371/journal.pone.0015718 Text en Hallböök et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hallböök, Helene
Felth, Jenny
Eriksson, Anna
Fryknäs, Mårten
Bohlin, Lars
Larsson, Rolf
Gullbo, Joachim
Ex Vivo Activity of Cardiac Glycosides in Acute Leukaemia
title Ex Vivo Activity of Cardiac Glycosides in Acute Leukaemia
title_full Ex Vivo Activity of Cardiac Glycosides in Acute Leukaemia
title_fullStr Ex Vivo Activity of Cardiac Glycosides in Acute Leukaemia
title_full_unstemmed Ex Vivo Activity of Cardiac Glycosides in Acute Leukaemia
title_short Ex Vivo Activity of Cardiac Glycosides in Acute Leukaemia
title_sort ex vivo activity of cardiac glycosides in acute leukaemia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3016342/
https://www.ncbi.nlm.nih.gov/pubmed/21246039
http://dx.doi.org/10.1371/journal.pone.0015718
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