Document Detail


Effectiveness of trichostatin A as a potential candidate for anticancer therapy in non-small-cell lung cancer.
MedLine Citation:
PMID:  16488717     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: A well-known histone deacetylase inhibitor, trichostatin A, was applied to non-small-cell lung cancer cells to determine whether inhibition of histone deacetylase leads to the production of proteins that either arrest tumor cell growth or lead to tumor cell death. METHODS: Trichostatin A (0.01 to 1.0 micromol/L) was applied to one normal lung fibroblast and four non-small-cell lung cancer lines, and its effect was determined by flow cytometry, annexin-V staining, immunoprecipitation, and Western blot analysis. RESULTS: Trichostatin A demonstrated tenfold greater growth inhibition in all four non-small-cell lung cancer lines compared with normal controls, with a concentration producing 50% inhibition ranging from 0.01 to 0.04 micromol/L for the tumor cell lines and 0.7 micromol/L for the normal lung fibroblast line. Trichostatin A treatment reduced the percentage of cells in S phase (10% to 23%) and increased G1 populations (10% to 40%) as determined by flow cytometry. Both annexin-V binding assay and upregulation of the protein, gelsolin (threefold to tenfold), demonstrated that the tumor cells were apoptotic, whereas normal cells were predominantly in cell cycle arrest. Trichostatin A increased histone H4 acetylation and expression of p21 twofold to 15-fold without significant effect on p16, p27, CDK2, and cyclin D1. CONCLUSIONS: Collectively, these data suggest that inhibition of histone deacetylation may provide a valuable approach for lung cancer treatment. We evaluated trichostatin A as a potential candidate for anticancer therapy in non-small-cell lung cancer.
Authors:
Nishit K Mukhopadhyay; Ellen Weisberg; David Gilchrist; Raphael Bueno; David J Sugarbaker; Michael T Jaklitsch
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Annals of thoracic surgery     Volume:  81     ISSN:  1552-6259     ISO Abbreviation:  Ann. Thorac. Surg.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-02-20     Completed Date:  2006-09-08     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  15030100R     Medline TA:  Ann Thorac Surg     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1034-42     Citation Subset:  AIM; IM    
Affiliation:
Division of Thoracic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. nmukhopadhyay@partners.org
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / therapeutic use*
Apoptosis / drug effects
Carcinoma, Non-Small-Cell Lung / drug therapy*,  pathology
Cell Cycle / drug effects
Cell Line
Cell Line, Tumor
Cell Survival / drug effects
Cyclin D1 / metabolism
Enzyme Inhibitors / therapeutic use
Gelsolin / metabolism
Histone Deacetylase Inhibitors
Histones / metabolism
Humans
Hydroxamic Acids / therapeutic use*
Lung / drug effects
Lung Neoplasms / drug therapy*,  pathology
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Enzyme Inhibitors; 0/Gelsolin; 0/Histone Deacetylase Inhibitors; 0/Histones; 0/Hydroxamic Acids; 136601-57-5/Cyclin D1; 58880-19-6/trichostatin A
Comments/Corrections
Comment In:
Ann Thorac Surg. 2006 Mar;81(3):1042   [PMID:  16488718 ]

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


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