Apoptin selectively induces the apoptosis of tumor cells by suppressing the transcription of HSP70
Apoptin is a nonstructural viral protein encoded by VP3 gene of chicken anemia virus, which could specially induce apoptosis of tumor cells. However, the mechanism of apoptin-induced apoptosis in tumor cells without any side effects in normal cells has not yet been well characterized. This study aim...
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| Veröffentlicht in: | Tumor biology 2013-02, Vol.34 (1), p.577-585 |
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| creator | Yuan, Lijie Zhang, Liqiu Dong, Xingli Zhao, Hengyu Li, Shuyan Han, Dong Liu, Xinghan |
| description | Apoptin is a nonstructural viral protein encoded by VP3 gene of chicken anemia virus, which could specially induce apoptosis of tumor cells. However, the mechanism of apoptin-induced apoptosis in tumor cells without any side effects in normal cells has not yet been well characterized. This study aimed to investigate the molecular mechanism underlying the selective antitumor effects of apoptin. HepG2 cells were treated with apoptin or transfected with apoptin expression vector. Heat shock protein 70 (HSP70) expression was examined by Western blot. The binding of apoptin to HSP70 promoter was detected by electrophoretic mobility shift assay, chromatin immunoprecipitation, and luciferase assay. The results showed that apoptin inhibited HSP70 expression in HepG2 cells and apoptin-induced apoptosis of HepG2 cells was dependent on the expression level of HSP70. Furthermore, apoptin promoted HSF1 trimer depolymerization and inhibited HSF1-mediated HSP70 transcription. In addition, apoptin competed with HSF1 to bind heat shock element in HSP70 promoter, leading to reduced HSP70 transcription. Both these mechanisms contribute to the suppression of HSP70 transcription and expression. Our findings provide the first evidence that apoptin induces tumor cell apoptosis by specifically downregulating the expression of HSP70, which helps explain the specific antitumor effects of apoptin. |
| doi_str_mv | 10.1007/s13277-012-0585-y |
| format | Article |
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However, the mechanism of apoptin-induced apoptosis in tumor cells without any side effects in normal cells has not yet been well characterized. This study aimed to investigate the molecular mechanism underlying the selective antitumor effects of apoptin. HepG2 cells were treated with apoptin or transfected with apoptin expression vector. Heat shock protein 70 (HSP70) expression was examined by Western blot. The binding of apoptin to HSP70 promoter was detected by electrophoretic mobility shift assay, chromatin immunoprecipitation, and luciferase assay. The results showed that apoptin inhibited HSP70 expression in HepG2 cells and apoptin-induced apoptosis of HepG2 cells was dependent on the expression level of HSP70. Furthermore, apoptin promoted HSF1 trimer depolymerization and inhibited HSF1-mediated HSP70 transcription. In addition, apoptin competed with HSF1 to bind heat shock element in HSP70 promoter, leading to reduced HSP70 transcription. Both these mechanisms contribute to the suppression of HSP70 transcription and expression. Our findings provide the first evidence that apoptin induces tumor cell apoptosis by specifically downregulating the expression of HSP70, which helps explain the specific antitumor effects of apoptin.</description><identifier>ISSN: 1010-4283</identifier><identifier>EISSN: 1423-0380</identifier><identifier>DOI: 10.1007/s13277-012-0585-y</identifier><identifier>PMID: 23179398</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Apoptosis ; Apoptosis - drug effects ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Capsid Proteins - metabolism ; Capsid Proteins - pharmacology ; Cell Line, Tumor ; Cells ; Chromatin Immunoprecipitation ; DNA-Binding Proteins - metabolism ; Down-Regulation ; Electrophoretic Mobility Shift Assay ; Heat Shock Transcription Factors ; Hep G2 Cells ; HSP70 Heat-Shock Proteins - biosynthesis ; HSP70 Heat-Shock Proteins - genetics ; Humans ; Liver Neoplasms ; Promoter Regions, Genetic ; Protein Multimerization - drug effects ; Proteins ; Research Article ; Transcription Factors - metabolism ; Transcription, Genetic ; Tumors</subject><ispartof>Tumor biology, 2013-02, Vol.34 (1), p.577-585</ispartof><rights>International Society of Oncology and BioMarkers (ISOBM) 2012</rights><rights>International Society of Oncology and BioMarkers (ISOBM) 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-e2fb25a3dce88ead17f4a1d4dfc667f5685c61f6d6cbcbc6187fbbb30bf00bbe3</citedby><cites>FETCH-LOGICAL-c372t-e2fb25a3dce88ead17f4a1d4dfc667f5685c61f6d6cbcbc6187fbbb30bf00bbe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s13277-012-0585-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s13277-012-0585-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23179398$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yuan, Lijie</creatorcontrib><creatorcontrib>Zhang, Liqiu</creatorcontrib><creatorcontrib>Dong, Xingli</creatorcontrib><creatorcontrib>Zhao, Hengyu</creatorcontrib><creatorcontrib>Li, Shuyan</creatorcontrib><creatorcontrib>Han, Dong</creatorcontrib><creatorcontrib>Liu, Xinghan</creatorcontrib><title>Apoptin selectively induces the apoptosis of tumor cells by suppressing the transcription of HSP70</title><title>Tumor biology</title><addtitle>Tumor Biol</addtitle><addtitle>Tumour Biol</addtitle><description>Apoptin is a nonstructural viral protein encoded by VP3 gene of chicken anemia virus, which could specially induce apoptosis of tumor cells. However, the mechanism of apoptin-induced apoptosis in tumor cells without any side effects in normal cells has not yet been well characterized. This study aimed to investigate the molecular mechanism underlying the selective antitumor effects of apoptin. HepG2 cells were treated with apoptin or transfected with apoptin expression vector. Heat shock protein 70 (HSP70) expression was examined by Western blot. The binding of apoptin to HSP70 promoter was detected by electrophoretic mobility shift assay, chromatin immunoprecipitation, and luciferase assay. The results showed that apoptin inhibited HSP70 expression in HepG2 cells and apoptin-induced apoptosis of HepG2 cells was dependent on the expression level of HSP70. Furthermore, apoptin promoted HSF1 trimer depolymerization and inhibited HSF1-mediated HSP70 transcription. In addition, apoptin competed with HSF1 to bind heat shock element in HSP70 promoter, leading to reduced HSP70 transcription. Both these mechanisms contribute to the suppression of HSP70 transcription and expression. Our findings provide the first evidence that apoptin induces tumor cell apoptosis by specifically downregulating the expression of HSP70, which helps explain the specific antitumor effects of apoptin.</description><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Capsid Proteins - metabolism</subject><subject>Capsid Proteins - pharmacology</subject><subject>Cell Line, Tumor</subject><subject>Cells</subject><subject>Chromatin Immunoprecipitation</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Down-Regulation</subject><subject>Electrophoretic Mobility Shift Assay</subject><subject>Heat Shock Transcription Factors</subject><subject>Hep G2 Cells</subject><subject>HSP70 Heat-Shock Proteins - biosynthesis</subject><subject>HSP70 Heat-Shock Proteins - genetics</subject><subject>Humans</subject><subject>Liver Neoplasms</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Multimerization - drug effects</subject><subject>Proteins</subject><subject>Research Article</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription, Genetic</subject><subject>Tumors</subject><issn>1010-4283</issn><issn>1423-0380</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kUFr3jAMhs1YWbtuP2CXYdill3SW_cV2jqVs66DQQbeziR25S8kXZ1YyyL-v068bozB0kECPXgm9jL0DcQ5CmI8EShpTCZCVqG1drS_YCeykqoSy4mWpBYhqJ606Zq-J7oWAumn0K3YsFZhGNfaE-YspTXM_csIBw9z_xmHl_dgtAYnPP5G3Wz9RTzxFPi_7lHnAYSDuV07LNGUk6se7R3bO7Ugh90UwjRt_dfvNiDfsKLYD4dunfMp-fP70_fKqur758vXy4roKysi5Qhm9rFvVBbQW2w5M3LXQ7boYtDax1rYOGqLudPAlNFgTvfdK-CiE96hO2dlBd8rp14I0u31P263tiGkhB9Io3dRCQUE_PEPv05LHct1GgbXlsXWh4ECFnIgyRjflft_m1YFwmwHuYIArBrjNALeWmfdPyovfY_d34s_HCyAPAJXWeIf5n9X_VX0AUPiTNw</recordid><startdate>20130201</startdate><enddate>20130201</enddate><creator>Yuan, Lijie</creator><creator>Zhang, Liqiu</creator><creator>Dong, Xingli</creator><creator>Zhao, Hengyu</creator><creator>Li, Shuyan</creator><creator>Han, Dong</creator><creator>Liu, Xinghan</creator><general>Springer Netherlands</general><general>Springer Nature B.V</general><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>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20130201</creationdate><title>Apoptin selectively induces the apoptosis of tumor cells by suppressing the transcription of HSP70</title><author>Yuan, Lijie ; Zhang, Liqiu ; Dong, Xingli ; Zhao, Hengyu ; Li, Shuyan ; Han, Dong ; Liu, Xinghan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-e2fb25a3dce88ead17f4a1d4dfc667f5685c61f6d6cbcbc6187fbbb30bf00bbe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Capsid Proteins - metabolism</topic><topic>Capsid Proteins - pharmacology</topic><topic>Cell Line, Tumor</topic><topic>Cells</topic><topic>Chromatin Immunoprecipitation</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Down-Regulation</topic><topic>Electrophoretic Mobility Shift Assay</topic><topic>Heat Shock Transcription Factors</topic><topic>Hep G2 Cells</topic><topic>HSP70 Heat-Shock Proteins - biosynthesis</topic><topic>HSP70 Heat-Shock Proteins - genetics</topic><topic>Humans</topic><topic>Liver Neoplasms</topic><topic>Promoter Regions, Genetic</topic><topic>Protein Multimerization - drug effects</topic><topic>Proteins</topic><topic>Research Article</topic><topic>Transcription Factors - metabolism</topic><topic>Transcription, Genetic</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yuan, Lijie</creatorcontrib><creatorcontrib>Zhang, Liqiu</creatorcontrib><creatorcontrib>Dong, Xingli</creatorcontrib><creatorcontrib>Zhao, Hengyu</creatorcontrib><creatorcontrib>Li, Shuyan</creatorcontrib><creatorcontrib>Han, Dong</creatorcontrib><creatorcontrib>Liu, Xinghan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Tumor biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yuan, Lijie</au><au>Zhang, Liqiu</au><au>Dong, Xingli</au><au>Zhao, Hengyu</au><au>Li, Shuyan</au><au>Han, Dong</au><au>Liu, Xinghan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Apoptin selectively induces the apoptosis of tumor cells by suppressing the transcription of HSP70</atitle><jtitle>Tumor biology</jtitle><stitle>Tumor Biol</stitle><addtitle>Tumour Biol</addtitle><date>2013-02-01</date><risdate>2013</risdate><volume>34</volume><issue>1</issue><spage>577</spage><epage>585</epage><pages>577-585</pages><issn>1010-4283</issn><eissn>1423-0380</eissn><abstract>Apoptin is a nonstructural viral protein encoded by VP3 gene of chicken anemia virus, which could specially induce apoptosis of tumor cells. However, the mechanism of apoptin-induced apoptosis in tumor cells without any side effects in normal cells has not yet been well characterized. This study aimed to investigate the molecular mechanism underlying the selective antitumor effects of apoptin. HepG2 cells were treated with apoptin or transfected with apoptin expression vector. Heat shock protein 70 (HSP70) expression was examined by Western blot. The binding of apoptin to HSP70 promoter was detected by electrophoretic mobility shift assay, chromatin immunoprecipitation, and luciferase assay. The results showed that apoptin inhibited HSP70 expression in HepG2 cells and apoptin-induced apoptosis of HepG2 cells was dependent on the expression level of HSP70. Furthermore, apoptin promoted HSF1 trimer depolymerization and inhibited HSF1-mediated HSP70 transcription. In addition, apoptin competed with HSF1 to bind heat shock element in HSP70 promoter, leading to reduced HSP70 transcription. Both these mechanisms contribute to the suppression of HSP70 transcription and expression. Our findings provide the first evidence that apoptin induces tumor cell apoptosis by specifically downregulating the expression of HSP70, which helps explain the specific antitumor effects of apoptin.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>23179398</pmid><doi>10.1007/s13277-012-0585-y</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Apoptosis Apoptosis - drug effects Biomedical and Life Sciences Biomedicine Cancer Research Capsid Proteins - metabolism Capsid Proteins - pharmacology Cell Line, Tumor Cells Chromatin Immunoprecipitation DNA-Binding Proteins - metabolism Down-Regulation Electrophoretic Mobility Shift Assay Heat Shock Transcription Factors Hep G2 Cells HSP70 Heat-Shock Proteins - biosynthesis HSP70 Heat-Shock Proteins - genetics Humans Liver Neoplasms Promoter Regions, Genetic Protein Multimerization - drug effects Proteins Research Article Transcription Factors - metabolism Transcription, Genetic Tumors |
| title | Apoptin selectively induces the apoptosis of tumor cells by suppressing the transcription of HSP70 |
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