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

Authors
Eldawud-R; Stueckle-TA; Manivannan-S; Elbaz-H; Chen-M; Rojanasakul-Y; Dinu-CZ
Source
Biosens Bioelectron 2014 Sep; 59:192-199
NIOSHTIC No.
20044221
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.
Keywords
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
Contact
Y.Rojanasakul, Department o fBasic Pharmaceutical Sciences, West Virginia University,POBox9530,Morgantown,WV26505
CODEN
BBIOE4
Publication Date
20140915
Document Type
Journal Article
Email Address
yrojan@hsc.wvu.edu
Fiscal Year
2014
NTIS Accession No.
NTIS Price
Identifying No.
M052014
ISSN
0956-5663
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
Biosensors and Bioelectronics
State
WV
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