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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.

SUBMITTER: Eldawud R

PROVIDER: S-EPMC4739845 | biostudies-other | 2014 Sep

REPOSITORIES: biostudies-other

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

Eldawud R R Stueckle T A TA Manivannan S S Elbaz H H Chen M M Rojanasakul Y Y Dinu C Z CZ

Biosensors & bioelectronics 20140326

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 ...[more]

PMID: 24727605

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Project description:IntroductionIn order to assess the significance of drug levels measured in intensive care medicine, clinical and forensic toxicology, as well as for therapeutic drug monitoring, it is essential that a comprehensive collection of data is readily available. Therefore, it makes sense to offer a carefully referenced compilation of therapeutic and toxic plasma concentration ranges, as well as half-lives, of a large number of drugs and other xenobiotics for quick and comprehensive information.MethodsData have been abstracted from original papers and text books, as well as from previous compilations, and have been completed with data collected in our own forensic and clinical toxicology laboratory. The data presented in the table and corresponding annotations have been developed over the past 20 years and longer. A previous compilation has been completely revised and updated. In addition, more than 170 substances, especially drugs that have been introduced to the market since 2003 as well as illegal drugs, which became known to cause intoxications, were added. All data were carefully referenced and more than 200 new references were included. Moreover, the annotations providing details were completely revised and more than 100 annotations were added.ResultsFor nearly 1,000 drugs and other xenobiotics, therapeutic ("normal") and, if data were available, toxic and comatose-fatal blood-plasma concentrations and elimination half-lives were compiled in a table.ConclusionsIn case of intoxications, the concentration of the ingested substances and/or metabolites in blood plasma better predicts the clinical severity of the case when compared to the assumed amount and time of ingestion. Comparing and contrasting the clinical case against the data provided, including the half-life, may support the decision for or against further intensive care. In addition, the data provided are useful for the therapeutic monitoring of pharmacotherapies, to facilitate the diagnostic assessment and monitoring of acute and chronic intoxications, and to support forensic and clinical expert opinions.

Dataset Information

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

Publications

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

Similar Datasets

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