Human tumor cell sensitivity to oleandrin is dependent on relative expression of Na+, K+-ATPase subunitsf

摘要

Cardiac glycosides have traditionally been used to treat congestive heart disease based on their selective ability to inhibit Na+, K+-ATPase and increase intrac-ellular Ca2+ concentrations, resulting in a positive ino-tropic effect. Recent studies have shown that inhibitors of Na+, K+-ATPase enzymatic activity also mediate changes in several intracellular signaling pathways. Inhibition of Na+, K+-ATPase by cardiac glycosides, for example, inactivates PKC and NF-kB pathways and increases reactive oxygen species (ROS) in cells leading to apoptosis (1-3). In addition, inhibition of Na+, K+-ATPase results in alterations of ion exchange which have been shown to affect cell adhesion and migration, as well as accumulation of certain drugs (4, 5). There is also clinical evidence demonstrating that Na+, K+-ATPase levels may themselves be an indicator of survival in renal clear cell carcinoma (3). These new findings indicate the potential for use of cardiac glycosides as cancer therapeutics.