(114b) Electronic Platform to Quantify the Anticancer Mechanisms of a Cardiac Glycoside and a Synthetic Analog

Digitoxin is a naturally occurring cardiac glycoside, well known for its efficiency in the treatment of congestive heart failure and arrhythmias. Recently, several reports have shown that digitoxin exhibits anti-neoplastic effects against several types of cancer ranging from breast to colon cancer, and from leukemia to lung cancer, suggesting digitoxin’s potential as a chemotherapeutic agent. The anticancer potency of digitoxin lies in its trisaccharide moiety which could be synthetically manipulated to produce  a library of analogues. In our research we used an electrical cell impedance sensing system (ECIS) as a proxy to assess the cellular behavior of immortalized and tumorigenic human lung cells (BEAS-2B and H460 respectively) upon exposure to digitoxin and a synthetic monosaccharide (D6-MA). Our highthroughput, non-invasive approach employed arrays with gold electrodes as immobilization platforms to measure the changes in cellular attachment, migration and cell-cell interactions in real time. The analysis was complemented by conventional microscopy techniques as well as cell-based assays to provide insights to the mechanistic anti-proliferative and pro-apoptotic signaling pathways activated by the drugs exposure. The results showed that both drugsselective anticancer mechanisms towards cancer cells and provided structure-function relationships that correlated the cellular dynamics with molecular pathways changes upon exposure. Our study provide novel means to investigate the underlying anticancer mechanism associated with natural or synthetic compounds and promises to help expedite the understanding of their anticancer mechanisms as well as facilitate their potential implementation as chemotherapeutic agent.

Disclaimer

These  findings and conclusions are those of the authors and do not necessarily represent the views of the National Institute for Occupational Safety and Health.