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Mammalian Cardenolides in Cancer Prevention and Therapeutics

Al-Ghoul, Mohammad PhD*; Valdes, Roland Jr PhD*†

doi: 10.1097/FTD.0b013e31816b90ff
Proceedings Paper

Digoxin-like immunoreactive factor (DLIF) and ouabain-like factor (OLF) are the mammalian counterparts to the plant-derived cardiotonic steroids digoxin and ouabain. Compelling evidence indicates that the cardiotonic steroids may have anticancer properties. Recent evidence indicates that low (nanomolar) concentrations of DLIF selectively induce cell death in transformed cells, while sparing normal cells, and is even more potent than the plant-derived compounds. The discovery that these endogenous molecules may play a role in the regulation of cancer cell proliferation provides a potentially new paradigm for the physiologic role of DLIF and OLF. In addition, the possible use of digoxin itself as a therapeutic agent in cancer has been explored, and evidence suggests that its conversion to dihydrodigoxin may be involved in regulating anticancer activity. The mechanism(s) for the pro-apoptotic property of these compounds is not known. In this brief review, we will discuss the proposed mechanism of action of digoxin, ouabain, DLIF, and OLF as anticancer compounds and discuss the effects that metabolic conversion to their dihydro-derivatives may have on this activity. From the perspective of therapeutic drug monitoring, these findings suggest some potential new challenges in the need to measure concentrations of digoxin and dihydrodigoxin as well as their endogenous counterparts DLIF and OLF in serum.

From the Departments of *Pathology and Laboratory Medicine and †Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY.

Received for publication November 20, 2007; accepted January 27, 2008.

Reprints: Dr. Roland Valdes Jr, PhD, Department of Pathology and Laboratory Medicine, University of Louisville School of Medicine, MDR Building, Room 222, 511 South Floyd Street, Louisville, KY 40292 (e-mail: rvaldes@louisville.edu).

© 2008 Lippincott Williams & Wilkins, Inc.