Date of Completion
Mark W. Peczuh
Cell and Developmental Biology | Cell Biology | Molecular Biology
The focus of this research is on cell migration and how it can be better understood through the use of small molecules that modulate cell migratory activity. The results have particular relevance in the realm of cancer pharmacology. Cardiac glycosides, which are known inhibitors of the eukaryotic Na+/K+-ATPase, have been determined to have antimigratory activities through the screening of several small molecule libraries. Here we investigate the antimigratory activities of the cardiac glycoside digitoxin as well as its analogs that we synthesized. Antimigratory activity was determined by conducting a wound closure assay with MDA-MB-231 human breast carcinoma cells. This antimigratory activity was compared to the inhibitory activity when Na+/K+-ATPase was treated with digitoxin and its analogs in a Na+/K+-ATPase assay. A coloration between wound closure activity Na+/K+-ATPase inhibitory activity provides evidence that cardiac glycosides inhibit cell migration through their interaction with the Na+/K+-ATPase protein. This research will provide the grounds to study the specific pathways in which Na+/K+-ATPase is linked to the regulation of cell migration.
Johnson, Joshua H., "Elucidating the Mechanism of Antimigratory Activity of Cardiac Glycosides" (2012). Honors Scholar Theses. 277.