title: Digitoxin, at concentrations commonly found in the plasma of cardiac patients, antagonizes etoposide and idarubicin activity in K562 leukemia cells.
abstract: 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.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Seville, 41011, Seville, Spain. mlopezlazaro@us.es
authors.forename: Miguel
authors.initials: M
authors.lastname: López-Lázaro
authors.forename: Nuria
authors.initials: N
authors.lastname: Pastor
authors.forename: Sami S
authors.initials: SS
authors.lastname: Azrak
authors.forename: Maria Jesús
authors.initials: MJ
authors.lastname: Ayuso
authors.forename: Felipe
authors.initials: F
authors.lastname: Cortés
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Austin
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D059005:Topoisomerase II Inhibitors; D000677:Amsacrine; D005047:Etoposide; D008942:Mitoxantrone; D004074:Digitoxin; D015255:Idarubicin