The Cardiac Glycosides Digitoxin, Digoxin and Ouabain Induce a Potent Inhibition of Glycolysis in Lung Cancer Cells

Abstract

Cardiac glycosides are promising anticancer drugs. We have recently shown that the cardiac glycosides digitoxin, digoxin and ouabain induce selective killing of lung cancer cells, and that the cytotoxicity of digitoxin against these cells occurs at concentrations below those observed in the plasma of cardiac patients treated with this drug (Oncogene, 2013. doi: 10.1038/onc.2013.229). Here we report that digitoxin, digoxin and ouabain induce a potent inhibition of glycolysis (glucose consumption and lactate production) in A549 cells at nanomolar concentrations. This inhibition was comparable to that observed with millimolar concentrations of the glycolysis inhibitor dichloroacetate, which is currently undergoing clinical trials for the treatment of cancer. Because platinum compounds are commonly used in the treatment of lung cancer, we tested the cytotoxicity of several combinations of cisplatin with each cardiac glycoside; these combinations induced synergistic, antagonistic or additive effects mainly depending on the order at which the drugs were added to the cells.