| Trichostatin A induces apoptosis in lung cancer cells via simultaneous activation of the death receptor-mediated and mitochondrial pathway? | |
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MedLine Citation:
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PMID: 17202837 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Trichostatin A (TSA), originally developed as an antifungal agent, is one of potent histone deacetylase (HDAC) inhibitors, which are known to cause growth arrest and apoptosis induction of transformed cells, including urinary bladder, breast, prostate, ovary, and colon cancers. However, the effect of HDAC inhibitors on human non-small cell lung cancer cells is not clearly known yet. Herein, we demonstrated that treatment of TSA resulted in a significant decrease of the viability of H157 cells in a dose-dependent manner, which was revealed as apoptosis accompanying with nuclear fragmentation and an increase in sub-G0/G1 fraction. In addition, it induced the expression of Fas/FasL, which further triggered the activation of caspase-8. Catalytic activation of caspase-9 and decreased expression of anti-apoptotic Bcl-2 and Bcl-XL proteins were observed in TSA-treated cells. Catalytic activation of caspase-3 by TSA was further confirmed by cleavage of pro-caspase-3 and intracellular substrates, including poly (ADP-ribose) polymerase (PARP) and inhibitor of caspase-activated deoxyribonuclease (ICAD). In addition, a characteristic phenomenon of mitochondrial dysfunction, including mitochondrial membrane potential transition and release of mitochondrial cytochrome c into the cytosol was apparent in TSA-treated cells. Taken together, our data indicate that inhibition of HDAC by TSA induces the apoptosis of H157 cells through signaling cascade of Fas/FasL-mediated extrinsic and mitochondria-mediated intrinsic caspases pathway. |
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Authors:
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Hak-Ryul Kim; Eun-Jung Kim; Sei-Hoon Yang; Eun-Taik Jeong; Channy Park; Jae-Hyung Lee; Myung-Ja Youn; Hong-Seob So; Raekil Park |
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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: Experimental & molecular medicine Volume: 38 ISSN: 1226-3613 ISO Abbreviation: Exp. Mol. Med. Publication Date: 2006 Dec |
Date Detail:
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Created Date: 2007-01-04 Completed Date: 2007-01-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9607880 Medline TA: Exp Mol Med Country: Korea (South) |
Other Details:
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Languages: eng Pagination: 616-24 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, Wonkwang University School of Medicine, Jeonbuk 570-749, Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylation Apoptosis / drug effects* Caspase 3 / metabolism Caspase 8 / metabolism Caspase 9 / metabolism Catalysis Cell Line, Tumor Enzyme Activation Histones / metabolism Humans Hydroxamic Acids / pharmacology* Lung Neoplasms / metabolism*, pathology* Mitochondria / drug effects*, metabolism* Protein Isoforms / metabolism Receptors, Death Domain / metabolism* Signal Transduction |
| Chemical | |
Reg. No./Substance:
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0/Histones; 0/Hydroxamic Acids; 0/Protein Isoforms; 0/Receptors, Death Domain; 58880-19-6/trichostatin A; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 8; EC 3.4.22.-/Caspase 9 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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