Digitoxin, at concentrations commonly found in the plasma of cardiac patients, antagonizes etoposide and idarubicin activity in K562 leukemia cells.
Digitoxin is used in the treatment of cardiac congestion and some types of cardiac arrhythmias. The mechanism of action of this cardiac glycoside suggested that it might antagonize the anticancer activity of topoisomerase II poisons. The present report shows that digitoxin, at concentrations commonly found in the plasma of cardiac patients, significantly reduced etoposide and idarubicin-induced topoisomerase II cleavable complexes in K562 leukemia cells. This may lead to a reduction in the anticancer effect of these two topoisomerase II poisons when they are used in the clinic concurrently with digitoxin.
López-Lázaro
Miguel
M
Department of Pharmacology, Faculty of Pharmacy, University of Seville, 41011, Seville, Spain. mlopezlazaro@us.es
Pastor
Nuria
N
Azrak
Sami S
SS
Ayuso
Maria Jesús
MJ
Cortés
Felipe
F
Austin
Caroline A
CA
D000677:Amsacrine / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004074:Digitoxin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006801:Humans; D015255:Idarubicin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008942:Mitoxantrone / Q000494:pharmacology; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
D000970:Antineoplastic Agents; D059005:Topoisomerase II Inhibitors; D000677:Amsacrine; D005047:Etoposide; D008942:Mitoxantrone; D004074:Digitoxin; D015255:Idarubicin