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

Details

• Alternative Title:
  Biosens Bioelectron
• Personal Author:
  Eldawud, R. ; Stueckle, T.A. ; Manivannan, S. ; Elbaz, H. ; Chen, M. ; Rojanasakul, Y. ; Dinu, C.Z.
• Description:
  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.
• Subjects:
  Anti-cancer Antineoplastic Agents Apoptosis Article Biosensing Techniques Carcinoma, Non-Small-Cell Lung Cardiotonic Agents Cell-based Sensing Cell Adhesion Cell Line, Tumor Digitoxin Humans Lung Lung Neoplasms Signal Transduction

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• Source:
  Biosens Bioelectron. 59:192-199.
• Pubmed ID:
  24727605
• Pubmed Central ID:
  PMC4739845
• Document Type:
  Journal Article
• Funding:
  CC999999/Intramural CDC HHS/United States
• Volume:
  59
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:e80b196f374bb9cead5f1260f3f9e5fc0298d9aa9ccc03bbe9dba0b8c9305fba
• Download URL:
  https://stacks.cdc.gov/view/cdc/37866/cdc_37866_DS1.pdf
• File Type:
  [PDF - 1.37 MB ]