Real-Time Analysis of the Effects of Sub-Therapeutic Concentrations of Digitoxin On Lung Cancer Cells

Real-Time Analysis of the Effects of Sub-Therapeutic Concentrations of Digitoxin on Lung Cancer Cells

Surya Manivannan, Reem Eldawud, and Cerasela Zoica Dinu

Department of Chemical Engineering, West Virginia University, Morgantown, WV 26505

Digitoxin is a cardioglycoside (CG) with anti-proliferative effects on cancer cells. Studies have shown that digitoxin's anticancer mechanism may be associated with its ability to induce apoptosis by inhibiting the Na⁺/K⁺-ATPase pump. However, its mechanisms at clinical concentrations are still subject to debate. Herein, a non-invasive technique called Electric Cell Impedance Sensing (ECIS) was used to assess the behavior of non-small cell lung cancer (NCl-H460) when exposed to therapeutically relevant digitoxin concentrations. ECIS allowed characterization in real-time of the impedance changes of cells immobilized onto gold electrodes. Further correlation with alterations in cellular morphology and attachment, as well as cell-cell interactions allowed identification of key cytotoxic players. ECIS evaluation was complemented by apoptosis, viability, and confocal microscopy assays. Results showed that exposure to digitoxin affects cell adhesion and cell-cell interactions in a dose-dependent manner. This study is the first to focus on determining effects of digitoxin on cell adhesion and cell-cell interactions in real time in NCI-H460 cancer cells, and opens up new perspectives for research on digitoxin's anti-cancer mechanism for therapeutic purposes.