| Induction of apoptosis by trichostatin A, a histone deacetylase inhibitor, is associated with inhibition of cyclooxygenase-2 activity in human non-small cell lung cancer cells. | |
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MedLine Citation:
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PMID: 16010430 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Although histone deacetylase (HDAC) inhibitors are emerging as a promising new treatment strategy in malignancy, how they exert their effect on human non-small cell lung cancer cells is as yet unclear. This study was undertaken to investigate the underlying mechanism of an HDAC inhibitor, Trichostatin A (TSA), -induced apoptosis in a human lung carcinoma cell line A549. The effects of this compound were also tested on cyclooxygenase (COX) activity. Treatment of A549 cells to TSA resulted in the inhibition of viability and the induction of apoptosis in a concentration-dependent manner, which could be proved by trypan blue counts, DAPI staining, agarose gel electrophoresis and flow cytometry analysis. Apoptosis of A549 cells by TSA was associated with a down-regulation of anti-apoptotic Bcl-2 protein and an up-regulation of pro-apoptotic Bax protein. TSA treatment induced the proteolytic activation of caspase-3 and caspase-9, and a concomitant degradation of poly(ADP-ribose)-polymerase protein. Furthermore, TSA decreased the levels of COX-2 mRNA and protein expression without significant changes in the levels of COX-1, which was correlated with an inhibition in prostaglandin E2 synthesis. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of TSA. |
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Authors:
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Yung Hyun Choi |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: International journal of oncology Volume: 27 ISSN: 1019-6439 ISO Abbreviation: Int. J. Oncol. Publication Date: 2005 Aug |
Date Detail:
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Created Date: 2005-07-12 Completed Date: 2005-12-23 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9306042 Medline TA: Int J Oncol Country: Greece |
Other Details:
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Languages: eng Pagination: 473-9 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, South Korea. choiyh@deu.ac.kr |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects* Blotting, Western Carcinoma, Non-Small-Cell Lung / enzymology, pathology Caspase 3 Caspase 9 Caspases / metabolism Cell Line, Tumor Cell Survival / drug effects DNA Fragmentation / drug effects Dinoprostone / metabolism Dose-Response Relationship, Drug Enzyme Inhibitors / pharmacology* Flow Cytometry Gene Expression Regulation, Enzymologic / drug effects Histone Deacetylase Inhibitors* Histone Deacetylases / metabolism Humans Hydroxamic Acids / pharmacology* Lung Neoplasms / enzymology, pathology Poly(ADP-ribose) Polymerases / metabolism Proto-Oncogene Proteins c-bcl-2 / metabolism Reverse Transcriptase Polymerase Chain Reaction |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Histone Deacetylase Inhibitors; 0/Hydroxamic Acids; 0/Proto-Oncogene Proteins c-bcl-2; 363-24-6/Dinoprostone; 58880-19-6/trichostatin A; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/CASP9 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 9; EC 3.4.22.-/Caspases; EC 3.5.1.98/Histone Deacetylases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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