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 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.


RESULTS
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.


CONCLUSIONS
It is suggested that further investigation regarding CGs may be focused on diagnoses like T- and B-precursor ALL.
Department of Haematology, University Hospital, Uppsala University, Uppsala, Sweden. helene.hallbook@medsci.uu.se
Helene
H
Hallböök
Jenny
J
Felth
Anna
A
Eriksson
Mårten
M
Fryknäs
Lars
L
Bohlin
Rolf
R
Larsson
Joachim
J
Gullbo
D000208:Acute Disease; D002301:Cardiac Glycosides / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology; D004074:Digitoxin / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D015448:Leukemia, B-Cell / Q000188:drug therapy; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D014176:Protein Biosynthesis / Q000187:drug effects; D013045:Species Specificity
D002301:Cardiac Glycosides; D004074:Digitoxin
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