Real-time analysis of the effects of toxic, therapeutic and sub-therapeutic concentrations of digitoxin on lung cancer cells.

Abstract

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.

• Authors: R Eldawud, T A Stueckle, S Manivannan, H Elbaz, M Chen, Y Rojanasakul, C Z Dinu
• Journal: Biosensors & bioelectronics (Biosens Bioelectron) Vol. 59 Pg. 192-9 (Sep 15 2014) ISSN: 1873-4235 [Electronic] England
• PMID: 24727605 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• Cardiotonic Agents
• Digitoxin

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Biosensing Techniques (methods)
• Carcinoma, Non-Small-Cell Lung (drug therapy, metabolism, pathology)
• Cardiotonic Agents (pharmacology)
• Cell Adhesion (drug effects)
• Cell Line, Tumor
• Digitoxin (pharmacology)
• Humans
• Lung (metabolism, pathology)
• Lung Neoplasms (drug therapy, metabolism, pathology)
• Signal Transduction (drug effects)