Real-time analysis of the effects of toxic, therapeutic and sub-therapeutic concentrations of digitoxin on lung cancer cells.
Eldawud-R; Stueckle-TA; Manivannan-S; Elbaz-H; Chen-M; Rojanasakul-Y; Dinu-CZ
Biosens Bioelectron 2014 Sep; 59:192-199
Digitoxin belongs to a naturally occurring class of cardiac glycosides (CG); digitoxin is clinically approved for heart failure and known for its anti-cancer effects against non-small lung cancer cells (NSCLC). However, concerns associated with its narrow therapeutic index and its concentration-dependent mechanism of action are rising. Thus, before digitoxin implementation in designing and developing safer and more effective CG-based anti-cancer therapies, its pharmacological and safety profiles need to be fully elucidated. In this research we used a combinatorial approach to evaluate the anti-cancer mechanisms of digitoxin in real-time. Our approach employed a non-invasive electric cell impedance sensing technique as a proxy to monitor NSCLC behavior post-exposure to toxic, therapeutic and sub-therapeutic concentrations of the drug. By developing structure-function combinatorial relations we showed that digitoxin targets cancer cells in a time and dose-dependant manner by activating pro-apoptotic and anti-proliferative signaling cascades that results in strengthening cellular adhesion and sequestration of key regulatory proliferation protein from the nucleus.
Cardiac-function; Cancer; Lung; Analytical-processes; Safety-measures; Chemical-properties; Chemical-composition; Monitoring-systems; Proteins; Cell-function; Cellular-function;
Author Keywords: Digitoxin; Cell-based sensing; Cell adhesion; Anti-cancer
Y.Rojanasakul, Department o fBasic Pharmaceutical Sciences, West Virginia University,POBox9530,Morgantown,WV26505
Biosensors and Bioelectronics