Digitoxin, at concentrations commonly found in the plasma of cardiac patients, antagonizes etoposide and idarubicin activity in K562 leukemia cells

Leuk Res. 2006 Jul;30(7):895-8. doi: 10.1016/j.leukres.2005.11.005. Epub 2006 Jan 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amsacrine / pharmacology
  • Antineoplastic Agents / pharmacology*
  • Digitoxin / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Etoposide / antagonists & inhibitors*
  • Etoposide / pharmacology
  • Humans
  • Idarubicin / antagonists & inhibitors*
  • Idarubicin / pharmacology
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Mitoxantrone / pharmacology
  • Structure-Activity Relationship
  • Topoisomerase II Inhibitors*

Substances

  • Antineoplastic Agents
  • Topoisomerase II Inhibitors
  • Amsacrine
  • Etoposide
  • Mitoxantrone
  • Digitoxin
  • Idarubicin