title: 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.affiliation: Department of Chemical Engineering, West Virginia University, WV, United States.
authors.forename: R
authors.initials: R
authors.lastname: Eldawud
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, WV, United States; Department of Basic Pharmaceutical Sciences, West Virginia University, WV, United States.
authors.forename: T A
authors.initials: TA
authors.lastname: Stueckle
authors.affiliation: Department of Chemical Engineering, West Virginia University, WV, United States.
authors.forename: S
authors.initials: S
authors.lastname: Manivannan
authors.affiliation: Wayne State University School of Medicine, MI, United States.
authors.forename: H
authors.initials: H
authors.lastname: Elbaz
authors.affiliation: Department of Basic Pharmaceutical Sciences, West Virginia University, WV, United States.
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Basic Pharmaceutical Sciences, West Virginia University, WV, United States; Mary Babb Randolph Cancer Center Allen Lung Program, West Virginia University, WV, United States. Electronic address: yrojan@hsc.wvu.edu.
authors.forename: Y
authors.initials: Y
authors.lastname: Rojanasakul
authors.affiliation: Department of Chemical Engineering, West Virginia University, WV, United States; Department of Basic Pharmaceutical Sciences, West Virginia University, WV, United States; Mary Babb Randolph Cancer Center Allen Lung Program, West Virginia University, WV, United States. Electronic address: cerasela-zoica.dinu@mail.wvu.edu.
authors.forename: C Z
authors.initials: CZ
authors.lastname: Dinu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015374:Biosensing Techniques / Q000379:methods; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002316:Cardiotonic Agents / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D004074:Digitoxin / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D002316:Cardiotonic Agents; D004074:Digitoxin
keywords: Anti-cancer; Cell adhesion; Cell-based sensing; Digitoxin
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