(622x) Old Dog New Tricks; Electronic Platform to Quantify the Anti-Cancer Potential of a Cardiac Glycoside and Its Synthetic Analogue in Real-Time

Authors: 
Gupta, N., WVU
Eldawud, R., West Virginia University
Rojanasakul, Y., West Virginia University
Dinu, C. Z., West Virginia University

Recent studies shows that digitoxin, a cardiac glycoside, exhibits strong anti-cancer effects with a high selectivity towards neoplastic cells when compared to normal cells. Previous research has also showed that the anticancer potency of digitoxin lays in its trisaccharide moiety with further manipulation of its structure leading to more potent analogues with different cellular mechanisms and possible clinical applications extended towards targeting lung, breast and leukemic cancers. In this research, we employed a new approach to characterize and quantify the cellular behavior of immortalized and tumorigenic human lung cells (BEAS-2B and H460 respectively) upon exposure to different concentrations of digitoxin and synthetic monosaccharide analogue (D6-MA) in real time. The approach relies on an electrical cell impedance sensing system (ECIS) used to monitor the morphological changes and cell-cell interactions in response to non-invasive electrical signals. Such measurements were further correlated with biophysical, microscopy and flow cytometry analyses to evaluate the cellular dynamics and the molecular pathways associated with exposure to the drug or analogue. Our results showed that both drugs target cancer cells in a time and dose-dependent manner by activating pro-apoptotic and anti-proliferative signaling cascades that result in strengthening cellular adhesion and sequestration of key regulatory proliferation proteins. Our study provides novel means to investigate the underlying anticancer mechanisms associated with exposure to natural or synthetic compounds and promises to help expedite the potential implementation of Digitoxin and its analogs as chemotherapeutic agents for cancer treatment.