PS-341 and histone deacetylase inhibitor synergistically induce apoptosis in head and neck squamous cell carcinoma cells
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 c...
Gespeichert in:
Veröffentlicht in: | Molecular cancer therapeutics 2010-07, Vol.9 (7), p.1977-1984 |
---|---|
Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 1984 |
---|---|
container_issue | 7 |
container_start_page | 1977 |
container_title | Molecular cancer therapeutics |
container_volume | 9 |
creator | Kim, Jinkoo Guan, Jean Chang, Insoon Chen, Xiaohong Han, Demin Wang, Cun-Yu |
description | 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. |
doi_str_mv | 10.1158/1535-7163.MCT-10-0141 |
format | Article |
fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2931416</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>20571067</sourcerecordid><originalsourceid>FETCH-LOGICAL-c410t-13b4ccaea914a297295d0b9a030a9ca267177bf0d20fe9cb115be36a7062efcd3</originalsourceid><addsrcrecordid>eNpVkdtOwzAQRC0EoqXwCSD_QIo3zqV5QUIVN6kIJMqztXE2rSGNS5wg-vc4LVTwZHt2ZyydYewcxBggnlxCLOMghUSOH6fzAEQgIIIDNvT6JJjEEB1u77udATtx7k0ImGQhHLNBKOIURJIO2dfzSyAj4FgXfGlca2viBaGmdlOhI27qpclNaxvuNjU1C79iNFbVxk-KThPHtV231hnnBb4kLLZRNel37j46XNnOcU1VxTU22tR2hdunO2VHJVaOzn7OEXu9vZlP74PZ093D9HoW6AhEG4DMI62RMIMIwywNs7gQeYZCCsw0hkkKaZqXoghFSZnOPZucZIKpSEIqdSFH7GqXu-7yFRWa6rbBSq0bs8Jmoywa9X9Sm6Va2E8VZtITTXxAvAvQjXWuoXLvBaH6KlSPWfWYla-iV_sqvO_i78d71y97-Q2pR4jI</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>PS-341 and histone deacetylase inhibitor synergistically induce apoptosis in head and neck squamous cell carcinoma cells</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>American Association for Cancer Research</source><creator>Kim, Jinkoo ; Guan, Jean ; Chang, Insoon ; Chen, Xiaohong ; Han, Demin ; Wang, Cun-Yu</creator><creatorcontrib>Kim, Jinkoo ; Guan, Jean ; Chang, Insoon ; Chen, Xiaohong ; Han, Demin ; Wang, Cun-Yu</creatorcontrib><description>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.</description><identifier>ISSN: 1535-7163</identifier><identifier>EISSN: 1538-8514</identifier><identifier>DOI: 10.1158/1535-7163.MCT-10-0141</identifier><identifier>PMID: 20571067</identifier><language>eng</language><publisher>United States</publisher><subject>Acetylation - drug effects ; Animals ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - pharmacology ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Apoptosis - drug effects ; Blotting, Northern ; Blotting, Western ; Boronic Acids - administration & dosage ; Boronic Acids - pharmacology ; Bortezomib ; Carcinoma, Squamous Cell - drug therapy ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Caspases - metabolism ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Drug Synergism ; Enzyme Activation - drug effects ; Head and Neck Neoplasms - drug therapy ; Head and Neck Neoplasms - metabolism ; Head and Neck Neoplasms - pathology ; Histone Deacetylase Inhibitors - administration & dosage ; Histone Deacetylase Inhibitors - pharmacology ; Histones - metabolism ; Humans ; Hydroxamic Acids - administration & dosage ; Hydroxamic Acids - pharmacology ; Mice ; Mice, Nude ; Proto-Oncogene Proteins c-bcl-2 - genetics ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Pyrazines - administration & dosage ; Pyrazines - pharmacology ; RNA Interference ; Xenograft Model Antitumor Assays</subject><ispartof>Molecular cancer therapeutics, 2010-07, Vol.9 (7), p.1977-1984</ispartof><rights>(c)2010 AACR.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c410t-13b4ccaea914a297295d0b9a030a9ca267177bf0d20fe9cb115be36a7062efcd3</citedby><cites>FETCH-LOGICAL-c410t-13b4ccaea914a297295d0b9a030a9ca267177bf0d20fe9cb115be36a7062efcd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,782,786,887,3358,27931,27932</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20571067$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Jinkoo</creatorcontrib><creatorcontrib>Guan, Jean</creatorcontrib><creatorcontrib>Chang, Insoon</creatorcontrib><creatorcontrib>Chen, Xiaohong</creatorcontrib><creatorcontrib>Han, Demin</creatorcontrib><creatorcontrib>Wang, Cun-Yu</creatorcontrib><title>PS-341 and histone deacetylase inhibitor synergistically induce apoptosis in head and neck squamous cell carcinoma cells</title><title>Molecular cancer therapeutics</title><addtitle>Mol Cancer Ther</addtitle><description>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.</description><subject>Acetylation - drug effects</subject><subject>Animals</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Apoptosis - drug effects</subject><subject>Blotting, Northern</subject><subject>Blotting, Western</subject><subject>Boronic Acids - administration & dosage</subject><subject>Boronic Acids - pharmacology</subject><subject>Bortezomib</subject><subject>Carcinoma, Squamous Cell - drug therapy</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Caspases - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Synergism</subject><subject>Enzyme Activation - drug effects</subject><subject>Head and Neck Neoplasms - drug therapy</subject><subject>Head and Neck Neoplasms - metabolism</subject><subject>Head and Neck Neoplasms - pathology</subject><subject>Histone Deacetylase Inhibitors - administration & dosage</subject><subject>Histone Deacetylase Inhibitors - pharmacology</subject><subject>Histones - metabolism</subject><subject>Humans</subject><subject>Hydroxamic Acids - administration & dosage</subject><subject>Hydroxamic Acids - pharmacology</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Proto-Oncogene Proteins c-bcl-2 - genetics</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Pyrazines - administration & dosage</subject><subject>Pyrazines - pharmacology</subject><subject>RNA Interference</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1535-7163</issn><issn>1538-8514</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkdtOwzAQRC0EoqXwCSD_QIo3zqV5QUIVN6kIJMqztXE2rSGNS5wg-vc4LVTwZHt2ZyydYewcxBggnlxCLOMghUSOH6fzAEQgIIIDNvT6JJjEEB1u77udATtx7k0ImGQhHLNBKOIURJIO2dfzSyAj4FgXfGlca2viBaGmdlOhI27qpclNaxvuNjU1C79iNFbVxk-KThPHtV231hnnBb4kLLZRNel37j46XNnOcU1VxTU22tR2hdunO2VHJVaOzn7OEXu9vZlP74PZ093D9HoW6AhEG4DMI62RMIMIwywNs7gQeYZCCsw0hkkKaZqXoghFSZnOPZucZIKpSEIqdSFH7GqXu-7yFRWa6rbBSq0bs8Jmoywa9X9Sm6Va2E8VZtITTXxAvAvQjXWuoXLvBaH6KlSPWfWYla-iV_sqvO_i78d71y97-Q2pR4jI</recordid><startdate>20100701</startdate><enddate>20100701</enddate><creator>Kim, Jinkoo</creator><creator>Guan, Jean</creator><creator>Chang, Insoon</creator><creator>Chen, Xiaohong</creator><creator>Han, Demin</creator><creator>Wang, Cun-Yu</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20100701</creationdate><title>PS-341 and histone deacetylase inhibitor synergistically induce apoptosis in head and neck squamous cell carcinoma cells</title><author>Kim, Jinkoo ; Guan, Jean ; Chang, Insoon ; Chen, Xiaohong ; Han, Demin ; Wang, Cun-Yu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c410t-13b4ccaea914a297295d0b9a030a9ca267177bf0d20fe9cb115be36a7062efcd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Acetylation - drug effects</topic><topic>Animals</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Apoptosis - drug effects</topic><topic>Blotting, Northern</topic><topic>Blotting, Western</topic><topic>Boronic Acids - administration & dosage</topic><topic>Boronic Acids - pharmacology</topic><topic>Bortezomib</topic><topic>Carcinoma, Squamous Cell - drug therapy</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Caspases - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Synergism</topic><topic>Enzyme Activation - drug effects</topic><topic>Head and Neck Neoplasms - drug therapy</topic><topic>Head and Neck Neoplasms - metabolism</topic><topic>Head and Neck Neoplasms - pathology</topic><topic>Histone Deacetylase Inhibitors - administration & dosage</topic><topic>Histone Deacetylase Inhibitors - pharmacology</topic><topic>Histones - metabolism</topic><topic>Humans</topic><topic>Hydroxamic Acids - administration & dosage</topic><topic>Hydroxamic Acids - pharmacology</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Proto-Oncogene Proteins c-bcl-2 - genetics</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><topic>Pyrazines - administration & dosage</topic><topic>Pyrazines - pharmacology</topic><topic>RNA Interference</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Jinkoo</creatorcontrib><creatorcontrib>Guan, Jean</creatorcontrib><creatorcontrib>Chang, Insoon</creatorcontrib><creatorcontrib>Chen, Xiaohong</creatorcontrib><creatorcontrib>Han, Demin</creatorcontrib><creatorcontrib>Wang, Cun-Yu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular cancer therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Jinkoo</au><au>Guan, Jean</au><au>Chang, Insoon</au><au>Chen, Xiaohong</au><au>Han, Demin</au><au>Wang, Cun-Yu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PS-341 and histone deacetylase inhibitor synergistically induce apoptosis in head and neck squamous cell carcinoma cells</atitle><jtitle>Molecular cancer therapeutics</jtitle><addtitle>Mol Cancer Ther</addtitle><date>2010-07-01</date><risdate>2010</risdate><volume>9</volume><issue>7</issue><spage>1977</spage><epage>1984</epage><pages>1977-1984</pages><issn>1535-7163</issn><eissn>1538-8514</eissn><abstract>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.</abstract><cop>United States</cop><pmid>20571067</pmid><doi>10.1158/1535-7163.MCT-10-0141</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1535-7163 |
ispartof | Molecular cancer therapeutics, 2010-07, Vol.9 (7), p.1977-1984 |
issn | 1535-7163 1538-8514 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2931416 |
source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research |
subjects | Acetylation - drug effects Animals Antineoplastic Agents - administration & dosage Antineoplastic Agents - pharmacology Antineoplastic Combined Chemotherapy Protocols - therapeutic use Apoptosis - drug effects Blotting, Northern Blotting, Western Boronic Acids - administration & dosage Boronic Acids - pharmacology Bortezomib Carcinoma, Squamous Cell - drug therapy Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Caspases - metabolism Cell Line, Tumor Dose-Response Relationship, Drug Drug Synergism Enzyme Activation - drug effects Head and Neck Neoplasms - drug therapy Head and Neck Neoplasms - metabolism Head and Neck Neoplasms - pathology Histone Deacetylase Inhibitors - administration & dosage Histone Deacetylase Inhibitors - pharmacology Histones - metabolism Humans Hydroxamic Acids - administration & dosage Hydroxamic Acids - pharmacology Mice Mice, Nude Proto-Oncogene Proteins c-bcl-2 - genetics Proto-Oncogene Proteins c-bcl-2 - metabolism Pyrazines - administration & dosage Pyrazines - pharmacology RNA Interference Xenograft Model Antitumor Assays |
title | PS-341 and histone deacetylase inhibitor synergistically induce apoptosis in head and neck squamous cell carcinoma cells |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-09T13%3A45%3A59IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=PS-341%20and%20histone%20deacetylase%20inhibitor%20synergistically%20induce%20apoptosis%20in%20head%20and%20neck%20squamous%20cell%20carcinoma%20cells&rft.jtitle=Molecular%20cancer%20therapeutics&rft.au=Kim,%20Jinkoo&rft.date=2010-07-01&rft.volume=9&rft.issue=7&rft.spage=1977&rft.epage=1984&rft.pages=1977-1984&rft.issn=1535-7163&rft.eissn=1538-8514&rft_id=info:doi/10.1158/1535-7163.MCT-10-0141&rft_dat=%3Cpubmed_cross%3E20571067%3C/pubmed_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/20571067&rfr_iscdi=true |