| PS-341 and histone deacetylase inhibitor synergistically induce apoptosis in head and neck squamous cell carcinoma cells. | |
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MedLine Citation:
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PMID: 20571067 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Proteasome inhibitor PS-341 (also known as bortezomib) and histone deacetylase (HDAC) inhibitors have emerged as novel therapeutic agents for a variety of malignancies. In this study, we examined whether PS-341 and the HDAC inhibitor trichostatin A (TSA) induced apoptosis in head and neck squamous cell carcinoma (HNSCC), a common and lethal malignancy. We found that, although TSA treatment alone did not induce apoptosis in HNSCC cells, it significantly enhanced PS-341-induced apoptosis in HNSCC cells in vitro. Consistently, TSA significantly improved PS-341-mediated inhibition of HNSCC tumor growth in nude mice. Mechanistically, we found that TSA increased PS-341-induced Noxa expression and caspase activation in HNSCC cells. The knockdown of Noxa significantly reduced apoptosis induced by cotreatment of PS-341 and TSA. Taken together, our results provide new insight into the mechanisms of synergistic antitumor activity of the PS-341 and HDAC inhibitor regimen, offering a new therapeutic strategy for HNSCC patients. |
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Authors:
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Jinkoo Kim; Jean Guan; Insoon Chang; Xiaohong Chen; Demin Han; Cun-Yu Wang |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-06-22 |
Journal Detail:
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Title: Molecular cancer therapeutics Volume: 9 ISSN: 1538-8514 ISO Abbreviation: Mol. Cancer Ther. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-09 Completed Date: 2010-11-04 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 101132535 Medline TA: Mol Cancer Ther Country: United States |
Other Details:
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Languages: eng Pagination: 1977-84 Citation Subset: IM |
Copyright Information:
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(c)2010 AACR. |
Affiliation:
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Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, California 90095, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetylation
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drug effects Animals Antineoplastic Agents / administration & dosage, pharmacology Antineoplastic Combined Chemotherapy Protocols / therapeutic use Apoptosis / drug effects* Blotting, Northern Blotting, Western Boronic Acids / administration & dosage, pharmacology* Carcinoma, Squamous Cell / drug therapy*, metabolism, pathology Caspases / metabolism Cell Line, Tumor Dose-Response Relationship, Drug Drug Synergism Enzyme Activation / drug effects Head and Neck Neoplasms / drug therapy*, metabolism, pathology Histone Deacetylase Inhibitors / administration & dosage, pharmacology Histones / metabolism Humans Hydroxamic Acids / administration & dosage, pharmacology* Mice Mice, Nude Proto-Oncogene Proteins c-bcl-2 / genetics, metabolism Pyrazines / administration & dosage, pharmacology* RNA Interference Xenograft Model Antitumor Assays |
| Grant Support | |
ID/Acronym/Agency:
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DE13848/DE/NIDCR NIH HHS; DE15964/DE/NIDCR NIH HHS; R01 DE015964-08/DE/NIDCR NIH HHS; R37 DE013848-11/DE/NIDCR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Boronic Acids; 0/Histone Deacetylase Inhibitors; 0/Histones; 0/Hydroxamic Acids; 0/PMAIP1 protein, human; 0/Proto-Oncogene Proteins c-bcl-2; 0/Pyrazines; 0/bortezomib; 58880-19-6/trichostatin A; EC 3.4.22.-/Caspases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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