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

Details

• Personal Author:
  Chen M ; Dinu CZ ; Elbaz H ; Eldawud R ; Manivannan S ; Rojanasakul Y ; Stueckle, Todd A.
• 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. [Description provided by NIOSH]
• Subjects:
  Cardiovascular System Chemistry Lung Neoplasms Occupational Health Respiratory System Safety Safety Management
• Keywords:
  Analytical-processes Anti-cancer Author Keywords: Digitoxin Cancer Cardiac-function Cell-based Sensing Cell-function Cell Adhesion Cellular-function Chemical-composition Chemical-properties Monitoring-systems Proteins Safety-measures

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• ISSN:
  0956-5663
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  192-199
• Volume:
  59
• NIOSHTIC Number:
  nn:20044221
• Citation:
  Biosens Bioelectron 2014 Sep; 59:192-199
• Contact Point Address:
  Y.Rojanasakul, Department o fBasic Pharmaceutical Sciences, West Virginia University,POBox9530,Morgantown,WV26505
• Email:
  yrojan@hsc.wvu.edu
• Federal Fiscal Year:
  2014
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Biosensors and Bioelectronics
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7288e1ee5217c991a5d8399f4d5f59f9a6e34ce5d7f1ac77e61dc68150356f1cb2e6aa0ffd5cdec35e414883a36622716073c8f13bdcd3530c9debe954620ebc
• Download URL:
  https://stacks.cdc.gov/view/cdc/199980/cdc_199980_DS1.pdf
• File Type:
  [PDF - 4.57 MB ]