Digitoxin as an anticancer agent with selectivity for cancer cells: possible mechanisms involved

Abstract

Accumulating preclinical and clinical data suggest that the cardiac drug digitoxin might be used in cancer therapy. Recent reports have shown that digitoxin can inhibit the growth and induce apoptosis in cancer cells at concentrations commonly found in the plasma of cardiac patients treated with this drug. Several mechanisms have been associated with the anticancer activity of digitoxin, yet at present it is unknown why malignant cells are more susceptible to this cardiac glycoside than non-malignant cells. This report analyses the possible anticancer mechanisms of digitoxin and proposes that the inhibition of glycolysis may be a key mechanism by which this natural product selectively targets cancer cells. Finally, whether or not there is enough evidence to support the clinical evaluation of digitoxin in patients with cancer is discussed.

Keywords::

• apoptosis
• cardenolide, cardiac glycoside
• digitalis
• dysoxia
• glycolysis
• hydrogen peroxide
• Na⁺/K⁺-ATPase
• renal cell carcinoma