Digitalis, a targeted therapy for cancer?
The clinical benefit of digitalis for patients with heart disease is well established. However, recent studies have also suggested that digitalis has antineoplastic activities at clinically relevant serum concentrations. Much of the early evidence supporting the anticancer activity of digitalis has been circumstantial. Observational studies suggest a protective benefit and improved outcomes in patients who develop cancer while they are taking digitalis. The mechanism by which digitalis selectively affects the growth of malignant cells is complex, involving several important signaling pathways. Experiments to determine its mechanism of action have demonstrated that digitalis inhibits cell growth and angiogenesis and induces apoptosis in multiple cancer cell lines. Most, if not all, of these effects are mediated through its target enzyme, sodium- and potassium-activated adenosine triphosphatase. This article reviews the literature, which supports the use of digitalis in patients with malignancies with a discussion of the potential mechanisms of action. We hypothesize that sodium- and potassium-activated adenosine triphosphatase is an important new target for cancer therapy. It is reasonable to expect that the addition of digitalis to current cancer treatments will improve the clinical outcomes.
Khan
M Iltaf
MI
Department of Medicine, Division of Medical Oncology and Hematology, University of Louisville, Louisville, KY 40202, USA.
Chesney
Jason A
JA
Laber
Damian A
DA
Miller
Donald M
DM
D000970:Antineoplastic Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004070:Digitalis / Q000378:metabolism; D004071:Digitalis Glycosides / Q000627:therapeutic use*; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008495:Medical Oncology / Q000639:trends; D009369:Neoplasms / Q000188:drug therapy*; D009389:Neovascularization, Pathologic; D010936:Plant Extracts / Q000627:therapeutic use; D015398:Signal Transduction; D016896:Treatment Outcome; D019061:src-Family Kinases / Q000378:metabolism
D000970:Antineoplastic Agents; D004071:Digitalis Glycosides; D010936:Plant Extracts; D019061:src-Family Kinases