| Effectiveness of trichostatin A as a potential candidate for anticancer therapy in non-small-cell lung cancer. | |
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MedLine Citation:
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PMID: 16488717 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Nishit K Mukhopadhyay; Ellen Weisberg; David Gilchrist; Raphael Bueno; David J Sugarbaker; Michael T Jaklitsch |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Annals of thoracic surgery Volume: 81 ISSN: 1552-6259 ISO Abbreviation: Ann. Thorac. Surg. Publication Date: 2006 Mar |
Date Detail:
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Created Date: 2006-02-20 Completed Date: 2006-09-08 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 15030100R Medline TA: Ann Thorac Surg Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1034-42 Citation Subset: AIM; IM |
Affiliation:
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Division of Thoracic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. nmukhopadhyay@partners.org |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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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:
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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:
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Ann Thorac Surg. 2006 Mar;81(3):1042
[PMID:
16488718
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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