Document Detail


Bioluminescence-based high-throughput screen identifies pharmacological agents that target neurotransmitter signaling in small cell lung carcinoma.
MedLine Citation:
PMID:  21931655     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Frontline treatment of small cell lung carcinoma (SCLC) relies heavily on chemotherapeutic agents and radiation therapy. Though SCLC patients respond well to initial cycles of chemotherapy, they eventually develop resistance. Identification of novel therapies against SCLC is therefore imperative.
METHODS AND FINDINGS: We have designed a bioluminescence-based cell viability assay for high-throughput screening of anti-SCLC agents. The assay was first validated via standard pharmacological agents and RNA interference using two human SCLC cell lines. We then utilized the assay in a high-throughput screen using the LOPAC(1280) compound library. The screening identified several drugs that target classic cancer signaling pathways as well as neuroendocrine markers in SCLC. In particular, perturbation of dopaminergic and serotonergic signaling inhibits SCLC cell viability.
CONCLUSIONS: The convergence of our pharmacological data with key SCLC pathway components reiterates the importance of neurotransmitter signaling in SCLC etiology and points to possible leads for drug development.
Authors:
Ma Reina D Improgo; Christopher W Johnson; Andrew R Tapper; Paul D Gardner
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-09-08
Journal Detail:
Title:  PloS one     Volume:  6     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2011  
Date Detail:
Created Date:  2011-09-20     Completed Date:  2012-03-01     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e24132     Citation Subset:  IM    
Affiliation:
Brudnick Neuropsychiatric Research Institute, Department of Psychiatry, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Survival / drug effects
Cisplatin / pharmacology
Dopamine Agents / pharmacology
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical / methods
Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / genetics
HEK293 Cells
Humans
Luciferases / genetics,  metabolism
Luminescent Measurements / methods*
Lung Neoplasms / genetics,  metabolism,  pathology
Mice
Neurotransmitter Agents / metabolism*
RNA Interference
Reverse Transcriptase Polymerase Chain Reaction
Serotonin Agents / pharmacology
Signal Transduction / drug effects*
Small Cell Lung Carcinoma / genetics,  metabolism,  pathology
Staurosporine / pharmacology
Time Factors
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Dopamine Agents; 0/Neurotransmitter Agents; 0/Serotonin Agents; 15663-27-1/Cisplatin; 62996-74-1/Staurosporine; EC 1.13.12.-/Luciferases; EC 1.2.1.12/Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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