RNA interference targeting Akt promotes apoptosis in hypoxia-exposed human neuroblastoma cells
Overactivation of the PI3 kinase/Akt pathway plays an essential role in the development and progression of various tumors. Akt is a key component of this pathway and hyperactivated in different tumors including neuroblastoma and glioma. In the present study, we tested the therapeutic efficacy of siR...
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Veröffentlicht in: | Brain research 2006-01, Vol.1070 (1), p.24-30 |
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description | Overactivation of the PI3 kinase/Akt pathway plays an essential role in the development and progression of various tumors. Akt is a key component of this pathway and hyperactivated in different tumors including neuroblastoma and glioma. In the present study, we tested the therapeutic efficacy of siRNA targeting Akt in inducing apoptotic cell death in NBFL cells (a human neuroblastoma cell line) subjected to anoxia/reoxygenation (A/R), a process that has been shown to modulate growth and progression of malignant tumors. We observed that siRNA targeting Akt effectively induced apoptotic cell death in NBFL cells (as determined by TUNEL assay and activated caspase-3 immunoreactivity) under normoxic conditions, an effect that was greatly enhanced under conditions of A/R. These findings underscore the importance of Akt signaling in promoting survival of neuroblastoma cells and may have potential therapeutic applications. |
doi_str_mv | 10.1016/j.brainres.2005.11.041 |
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Akt is a key component of this pathway and hyperactivated in different tumors including neuroblastoma and glioma. In the present study, we tested the therapeutic efficacy of siRNA targeting Akt in inducing apoptotic cell death in NBFL cells (a human neuroblastoma cell line) subjected to anoxia/reoxygenation (A/R), a process that has been shown to modulate growth and progression of malignant tumors. We observed that siRNA targeting Akt effectively induced apoptotic cell death in NBFL cells (as determined by TUNEL assay and activated caspase-3 immunoreactivity) under normoxic conditions, an effect that was greatly enhanced under conditions of A/R. These findings underscore the importance of Akt signaling in promoting survival of neuroblastoma cells and may have potential therapeutic applications.</description><identifier>ISSN: 0006-8993</identifier><identifier>EISSN: 1872-6240</identifier><identifier>DOI: 10.1016/j.brainres.2005.11.041</identifier><identifier>PMID: 16405925</identifier><identifier>CODEN: BRREAP</identifier><language>eng</language><publisher>London: Elsevier B.V</publisher><subject>Akt ; Anoxia ; Apoptosis ; Biological and medical sciences ; Cell Hypoxia ; Cell Line, Tumor ; Humans ; Medical sciences ; Molecular Sequence Data ; Neuroblastoma ; Neuroblastoma - genetics ; Neuroblastoma - metabolism ; Neuroblastoma - pathology ; Neuroblastoma - physiopathology ; Neurology ; Oxygen - pharmacology ; Proto-Oncogene Proteins c-akt - genetics ; Proto-Oncogene Proteins c-akt - metabolism ; RNA Interference ; RNAi ; Tumors of the nervous system. Phacomatoses ; Up-Regulation</subject><ispartof>Brain research, 2006-01, Vol.1070 (1), p.24-30</ispartof><rights>2005</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c427t-c7593b528b6a872199b0da760ab9ae5d62ef33027537aa591e42dceb1fcdcd783</citedby><cites>FETCH-LOGICAL-c427t-c7593b528b6a872199b0da760ab9ae5d62ef33027537aa591e42dceb1fcdcd783</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.brainres.2005.11.041$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,782,786,3554,27933,27934,46004</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17568408$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16405925$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Xiu-Huai</creatorcontrib><creatorcontrib>Yu, Erik Z.</creatorcontrib><creatorcontrib>Li, Ying-Yue</creatorcontrib><creatorcontrib>Rollwagen, Florence M.</creatorcontrib><creatorcontrib>Kagan, Elliott</creatorcontrib><title>RNA interference targeting Akt promotes apoptosis in hypoxia-exposed human neuroblastoma cells</title><title>Brain research</title><addtitle>Brain Res</addtitle><description>Overactivation of the PI3 kinase/Akt pathway plays an essential role in the development and progression of various tumors. Akt is a key component of this pathway and hyperactivated in different tumors including neuroblastoma and glioma. In the present study, we tested the therapeutic efficacy of siRNA targeting Akt in inducing apoptotic cell death in NBFL cells (a human neuroblastoma cell line) subjected to anoxia/reoxygenation (A/R), a process that has been shown to modulate growth and progression of malignant tumors. We observed that siRNA targeting Akt effectively induced apoptotic cell death in NBFL cells (as determined by TUNEL assay and activated caspase-3 immunoreactivity) under normoxic conditions, an effect that was greatly enhanced under conditions of A/R. These findings underscore the importance of Akt signaling in promoting survival of neuroblastoma cells and may have potential therapeutic applications.</description><subject>Akt</subject><subject>Anoxia</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>Cell Hypoxia</subject><subject>Cell Line, Tumor</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Molecular Sequence Data</subject><subject>Neuroblastoma</subject><subject>Neuroblastoma - genetics</subject><subject>Neuroblastoma - metabolism</subject><subject>Neuroblastoma - pathology</subject><subject>Neuroblastoma - physiopathology</subject><subject>Neurology</subject><subject>Oxygen - pharmacology</subject><subject>Proto-Oncogene Proteins c-akt - genetics</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>RNA Interference</subject><subject>RNAi</subject><subject>Tumors of the nervous system. Phacomatoses</subject><subject>Up-Regulation</subject><issn>0006-8993</issn><issn>1872-6240</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAQhi0EotvCK1S-wC3B4yR2cmNVFahUgYTgijVxJq2XJA62g9q3J9Eu6rEna6Rvxv_Mx9gliBwEqA-HvA3opkAxl0JUOUAuSnjBdlBrmSlZipdsJ4RQWd00xRk7j_GwlkXRiNfsDFQpqkZWO_br-9c9d1Oi0FOgyRJPGO4ouemO738nPgc_-kSR4-zn5KOLK83vH2f_4DCjh9lH6vj9MuLEJ1qCbweMyY_ILQ1DfMNe9ThEent6L9jPT9c_rr5kt98-31ztbzNbSp0yq6umaCtZtwrX_NA0rehQK4Ftg1R1SlJfFELqqtCIVQNUys5SC73tbKfr4oK9P85d8_5ZKCYzurglwIn8Eo3SSkMt5LMgaAAQegPVEbTBxxioN3NwI4ZHA8JsCszB_FdgNgUGwKwK1sbL0w9LO1L31Ha6-Qq8OwEYLQ59wMm6-MTpStWl2Hb6eORoPdxfR8FE6zZFnQtkk-m8ey7LP-Nlqbk</recordid><startdate>20060127</startdate><enddate>20060127</enddate><creator>Liu, Xiu-Huai</creator><creator>Yu, Erik Z.</creator><creator>Li, Ying-Yue</creator><creator>Rollwagen, Florence M.</creator><creator>Kagan, Elliott</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><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>7QO</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20060127</creationdate><title>RNA interference targeting Akt promotes apoptosis in hypoxia-exposed human neuroblastoma cells</title><author>Liu, Xiu-Huai ; Yu, Erik Z. ; Li, Ying-Yue ; Rollwagen, Florence M. ; Kagan, Elliott</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c427t-c7593b528b6a872199b0da760ab9ae5d62ef33027537aa591e42dceb1fcdcd783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Akt</topic><topic>Anoxia</topic><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>Cell Hypoxia</topic><topic>Cell Line, Tumor</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Molecular Sequence Data</topic><topic>Neuroblastoma</topic><topic>Neuroblastoma - genetics</topic><topic>Neuroblastoma - metabolism</topic><topic>Neuroblastoma - pathology</topic><topic>Neuroblastoma - physiopathology</topic><topic>Neurology</topic><topic>Oxygen - pharmacology</topic><topic>Proto-Oncogene Proteins c-akt - genetics</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>RNA Interference</topic><topic>RNAi</topic><topic>Tumors of the nervous system. Phacomatoses</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Xiu-Huai</creatorcontrib><creatorcontrib>Yu, Erik Z.</creatorcontrib><creatorcontrib>Li, Ying-Yue</creatorcontrib><creatorcontrib>Rollwagen, Florence M.</creatorcontrib><creatorcontrib>Kagan, Elliott</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Xiu-Huai</au><au>Yu, Erik Z.</au><au>Li, Ying-Yue</au><au>Rollwagen, Florence M.</au><au>Kagan, Elliott</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RNA interference targeting Akt promotes apoptosis in hypoxia-exposed human neuroblastoma cells</atitle><jtitle>Brain research</jtitle><addtitle>Brain Res</addtitle><date>2006-01-27</date><risdate>2006</risdate><volume>1070</volume><issue>1</issue><spage>24</spage><epage>30</epage><pages>24-30</pages><issn>0006-8993</issn><eissn>1872-6240</eissn><coden>BRREAP</coden><abstract>Overactivation of the PI3 kinase/Akt pathway plays an essential role in the development and progression of various tumors. Akt is a key component of this pathway and hyperactivated in different tumors including neuroblastoma and glioma. In the present study, we tested the therapeutic efficacy of siRNA targeting Akt in inducing apoptotic cell death in NBFL cells (a human neuroblastoma cell line) subjected to anoxia/reoxygenation (A/R), a process that has been shown to modulate growth and progression of malignant tumors. We observed that siRNA targeting Akt effectively induced apoptotic cell death in NBFL cells (as determined by TUNEL assay and activated caspase-3 immunoreactivity) under normoxic conditions, an effect that was greatly enhanced under conditions of A/R. These findings underscore the importance of Akt signaling in promoting survival of neuroblastoma cells and may have potential therapeutic applications.</abstract><cop>London</cop><cop>Amsterdam</cop><cop>New York, NY</cop><pub>Elsevier B.V</pub><pmid>16405925</pmid><doi>10.1016/j.brainres.2005.11.041</doi><tpages>7</tpages></addata></record> |
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subjects | Akt Anoxia Apoptosis Biological and medical sciences Cell Hypoxia Cell Line, Tumor Humans Medical sciences Molecular Sequence Data Neuroblastoma Neuroblastoma - genetics Neuroblastoma - metabolism Neuroblastoma - pathology Neuroblastoma - physiopathology Neurology Oxygen - pharmacology Proto-Oncogene Proteins c-akt - genetics Proto-Oncogene Proteins c-akt - metabolism RNA Interference RNAi Tumors of the nervous system. Phacomatoses Up-Regulation |
title | RNA interference targeting Akt promotes apoptosis in hypoxia-exposed human neuroblastoma cells |
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