Cardiac glycosides as novel cancer therapeutic agents.
The class of steroid-like compounds designated cardiac glycosides includes well-known drugs such as digoxin, digitoxin, and ouabain. Their continued efficacy in treatment of congestive heart failure and as anti-arrhythmic agents is well appreciated. Less well known, however, is the emerging role of this category of compounds in the prevention and/or treatment of proliferative diseases such as cancer. New findings within the past five years have revealed these compounds to be involved in complex cell-signal transduction mechanisms, resulting in selective control of human tumor but not normal cellular proliferation. As such, they represent a promising form of targeted cancer chemotherapy. New clinical studies of their anticancer potential as single or adjuvant treatments may provide insight into these potentially valuable therapeutic options. This review focuses on recent findings on cellular pharmacology of cardiac glycosides as they relate to treatment of human cancer and attempts to explain why these agents have been overlooked in the past.
Newman
Robert A
RA
Department of Experimental Therapeutics and Pharmaceutical Development Center, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77054, USA. rnewman@mdanderson.org
Yang
Peiying
P
Pawlus
Alison D
AD
Block
Keith I
KI
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D002301:Cardiac Glycosides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D015195:Drug Design; D006131:Growth Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000517:prevention & control; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology; D013045:Species Specificity
D000970:Antineoplastic Agents; D002301:Cardiac Glycosides; D006131:Growth Inhibitors; D011960:Receptors, Estrogen; D000254:Sodium-Potassium-Exchanging ATPase