Electronic Platform To Quantify The Anticancer Mechanisms Of Cardiac Glycoside and Synthetic Analog

The clinical applications of digitoxin as a cardiac glycoside have been halted by many concerns associated with its cardiac toxicity. Recently it was shown that the toxic profiles induced by therapeutic ranges of digitoxin exposure are selective to many types of neoplastic cells from breast to prostate and lung cancer, making this drug an attractive candidate for chemotherapies. The anticancer potency of digitoxin lays in its trisaccharide moiety linked to a steroid core. Further research has shown that synthetic manipulation of digitoxin structure leads to more potent analogues. In this research, a new approach is used 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 as a proxy to measure the morphological changes and cell-cell interactions in vitro. Such measurements are supplemented with biophysical techniques for multiparametric analysis to derive structure function relations that correlate the cellular dynamics with molecular pathways upon drug or analogue exposure. Our results provided novel means to investigate the underlying anticancer mechanisms associated with drug exposure at a single cells level and promise to extend such cellular-based interface studies to other analysts and toxins.

Disclaimer: The findings and conclusions in this abstract are those of the authors and do not necessarily represent the views of the National Institute for Occupational Safety and Health.