EZH2 mediates ATO-induced apoptosis in acute myeloid leukemia cell lines through the Wnt signaling pathway
In this study, we examined the mechanisms associated with EZH2 mediation of apoptosis and chemoresistance to arsenic trioxide (ATO) in acute myeloid leukemia (AML) cell lines through the Wnt/β-catenin signaling pathway. The induction of spontaneous apoptosis observed in multiple EZH2-silenced leukem...
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Veröffentlicht in: | Tumor biology 2016-05, Vol.37 (5), p.5919-5923 |
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description | In this study, we examined the mechanisms associated with EZH2 mediation of apoptosis and chemoresistance to arsenic trioxide (ATO) in acute myeloid leukemia (AML) cell lines through the Wnt/β-catenin signaling pathway. The induction of spontaneous apoptosis observed in multiple EZH2-silenced leukemic cell lines was assessed by flow cytometry, and levels of Wnt/β-catenin-related expression were determined by western blot analysis. In comparison with AML control cells, EZH2-knockdown cells exhibited increased apoptosis and significant downregulation of β-catenin expression, as well as decreases in GSK-3β phosphorylation and β-catenin activation (
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p
< 0.05 for all measurements). Additionally, EZH2 knockdown sensitized AML cells to induced cell death following administration of chemotherapeutic ATO. Our results suggested that EZH2 in leukemic cell lines might inhibit ATO-induced apoptosis and that EZH2 may be a potential therapeutic target in AML patients undergoing ATO treatment. Our findings provide new insights into the role of ATO and EZH2 in regulating AML progression.</description><identifier>ISSN: 1010-4283</identifier><identifier>EISSN: 1423-0380</identifier><identifier>DOI: 10.1007/s13277-015-4463-2</identifier><identifier>PMID: 26592252</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Antineoplastic Agents - pharmacology ; Apoptosis ; Apoptosis - drug effects ; Arsenicals - pharmacology ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Cell Line, Tumor ; Drug Resistance, Neoplasm - drug effects ; Enhancer of Zeste Homolog 2 Protein - genetics ; Enhancer of Zeste Homolog 2 Protein - metabolism ; Flow cytometry ; Gene Expression ; Gene Knockdown Techniques ; Glycogen Synthase Kinase 3 beta - metabolism ; HL-60 Cells ; Humans ; Leukemia ; Leukemia, Myeloid, Acute - genetics ; Leukemia, Myeloid, Acute - metabolism ; Original Article ; Oxides - pharmacology ; Phosphorylation ; Studies ; Wnt Signaling Pathway - drug effects</subject><ispartof>Tumor biology, 2016-05, Vol.37 (5), p.5919-5923</ispartof><rights>International Society of Oncology and BioMarkers (ISOBM) 2015</rights><rights>International Society of Oncology and BioMarkers (ISOBM) 2016</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c405t-1d4019c7e47663560acc0ce71e0f2312475c44f0ae90c67110049b436f2409b93</citedby><cites>FETCH-LOGICAL-c405t-1d4019c7e47663560acc0ce71e0f2312475c44f0ae90c67110049b436f2409b93</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/s13277-015-4463-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s13277-015-4463-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26592252$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Hao</creatorcontrib><creatorcontrib>Gu, Huizi</creatorcontrib><creatorcontrib>Li, Limei</creatorcontrib><creatorcontrib>Ren, Yuan</creatorcontrib><creatorcontrib>Zhang, Lijun</creatorcontrib><title>EZH2 mediates ATO-induced apoptosis in acute myeloid leukemia cell lines through the Wnt signaling pathway</title><title>Tumor biology</title><addtitle>Tumor Biol</addtitle><addtitle>Tumour Biol</addtitle><description>In this study, we examined the mechanisms associated with EZH2 mediation of apoptosis and chemoresistance to arsenic trioxide (ATO) in acute myeloid leukemia (AML) cell lines through the Wnt/β-catenin signaling pathway. The induction of spontaneous apoptosis observed in multiple EZH2-silenced leukemic cell lines was assessed by flow cytometry, and levels of Wnt/β-catenin-related expression were determined by western blot analysis. In comparison with AML control cells, EZH2-knockdown cells exhibited increased apoptosis and significant downregulation of β-catenin expression, as well as decreases in GSK-3β phosphorylation and β-catenin activation (
p
< 0.05 for all measurements). Additionally, EZH2 knockdown sensitized AML cells to induced cell death following administration of chemotherapeutic ATO. Our results suggested that EZH2 in leukemic cell lines might inhibit ATO-induced apoptosis and that EZH2 may be a potential therapeutic target in AML patients undergoing ATO treatment. Our findings provide new insights into the role of ATO and EZH2 in regulating AML progression.</description><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Arsenicals - pharmacology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Cell Line, Tumor</subject><subject>Drug Resistance, Neoplasm - drug effects</subject><subject>Enhancer of Zeste Homolog 2 Protein - genetics</subject><subject>Enhancer of Zeste Homolog 2 Protein - metabolism</subject><subject>Flow cytometry</subject><subject>Gene Expression</subject><subject>Gene Knockdown Techniques</subject><subject>Glycogen Synthase Kinase 3 beta - metabolism</subject><subject>HL-60 Cells</subject><subject>Humans</subject><subject>Leukemia</subject><subject>Leukemia, Myeloid, Acute - genetics</subject><subject>Leukemia, Myeloid, Acute - metabolism</subject><subject>Original Article</subject><subject>Oxides - pharmacology</subject><subject>Phosphorylation</subject><subject>Studies</subject><subject>Wnt Signaling Pathway - drug effects</subject><issn>1010-4283</issn><issn>1423-0380</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUlrHDEQhUWwiZfkB_hiBL74ori0tNQ6GuMlYPDFIZCL0KirZzTuza1uzPz7aGgnhEDIqQrqe6-keoSccfjCAcxV4lIYw4AXTCktmfhAjrkSkoEs4SD3wIEpUcojcpLSFjJorf5IjoQurBCFOCbb2x8PgrZYRT9hotfPTyx21Rywon7oh6lPMdHYUR_mCWm7w6aPFW1wfsE2ehqwaWgTuyydNmM_rze5Iv3eTTTFdefzaE0HP23e_O4TOax9k_Dzez0l3-5un28e2OPT_deb60cWFBQT45UCboNBZbSWhQYfAgQ0HKEWkgtliqBUDR4tBG14voSyKyV1LRTYlZWn5HLxHcb-dcY0uTam_UN9h_2cHC-h1EoqZf6PGgv5sErojF78hW77ecw_XCheSFOWmeILFcY-pRFrN4yx9ePOcXD7zNySmcsCt8_Miaw5f3eeVzmI34pfIWVALEDKo26N4x-r_-n6E9wWn0I</recordid><startdate>20160501</startdate><enddate>20160501</enddate><creator>Zhang, Hao</creator><creator>Gu, Huizi</creator><creator>Li, Limei</creator><creator>Ren, Yuan</creator><creator>Zhang, Lijun</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>7T5</scope><scope>7TO</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>20160501</creationdate><title>EZH2 mediates ATO-induced apoptosis in acute myeloid leukemia cell lines through the Wnt signaling pathway</title><author>Zhang, Hao ; Gu, Huizi ; Li, Limei ; Ren, Yuan ; Zhang, Lijun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c405t-1d4019c7e47663560acc0ce71e0f2312475c44f0ae90c67110049b436f2409b93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Arsenicals - pharmacology</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Cell Line, Tumor</topic><topic>Drug Resistance, Neoplasm - drug effects</topic><topic>Enhancer of Zeste Homolog 2 Protein - genetics</topic><topic>Enhancer of Zeste Homolog 2 Protein - metabolism</topic><topic>Flow cytometry</topic><topic>Gene Expression</topic><topic>Gene Knockdown Techniques</topic><topic>Glycogen Synthase Kinase 3 beta - metabolism</topic><topic>HL-60 Cells</topic><topic>Humans</topic><topic>Leukemia</topic><topic>Leukemia, Myeloid, Acute - genetics</topic><topic>Leukemia, Myeloid, Acute - metabolism</topic><topic>Original Article</topic><topic>Oxides - pharmacology</topic><topic>Phosphorylation</topic><topic>Studies</topic><topic>Wnt Signaling Pathway - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Hao</creatorcontrib><creatorcontrib>Gu, Huizi</creatorcontrib><creatorcontrib>Li, Limei</creatorcontrib><creatorcontrib>Ren, Yuan</creatorcontrib><creatorcontrib>Zhang, Lijun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Tumor biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Hao</au><au>Gu, Huizi</au><au>Li, Limei</au><au>Ren, Yuan</au><au>Zhang, Lijun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>EZH2 mediates ATO-induced apoptosis in acute myeloid leukemia cell lines through the Wnt signaling pathway</atitle><jtitle>Tumor biology</jtitle><stitle>Tumor Biol</stitle><addtitle>Tumour Biol</addtitle><date>2016-05-01</date><risdate>2016</risdate><volume>37</volume><issue>5</issue><spage>5919</spage><epage>5923</epage><pages>5919-5923</pages><issn>1010-4283</issn><eissn>1423-0380</eissn><abstract>In this study, we examined the mechanisms associated with EZH2 mediation of apoptosis and chemoresistance to arsenic trioxide (ATO) in acute myeloid leukemia (AML) cell lines through the Wnt/β-catenin signaling pathway. The induction of spontaneous apoptosis observed in multiple EZH2-silenced leukemic cell lines was assessed by flow cytometry, and levels of Wnt/β-catenin-related expression were determined by western blot analysis. In comparison with AML control cells, EZH2-knockdown cells exhibited increased apoptosis and significant downregulation of β-catenin expression, as well as decreases in GSK-3β phosphorylation and β-catenin activation (
p
< 0.05 for all measurements). Additionally, EZH2 knockdown sensitized AML cells to induced cell death following administration of chemotherapeutic ATO. Our results suggested that EZH2 in leukemic cell lines might inhibit ATO-induced apoptosis and that EZH2 may be a potential therapeutic target in AML patients undergoing ATO treatment. Our findings provide new insights into the role of ATO and EZH2 in regulating AML progression.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>26592252</pmid><doi>10.1007/s13277-015-4463-2</doi><tpages>5</tpages></addata></record> |
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subjects | Antineoplastic Agents - pharmacology Apoptosis Apoptosis - drug effects Arsenicals - pharmacology Biomedical and Life Sciences Biomedicine Cancer Research Cell Line, Tumor Drug Resistance, Neoplasm - drug effects Enhancer of Zeste Homolog 2 Protein - genetics Enhancer of Zeste Homolog 2 Protein - metabolism Flow cytometry Gene Expression Gene Knockdown Techniques Glycogen Synthase Kinase 3 beta - metabolism HL-60 Cells Humans Leukemia Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - metabolism Original Article Oxides - pharmacology Phosphorylation Studies Wnt Signaling Pathway - drug effects |
title | EZH2 mediates ATO-induced apoptosis in acute myeloid leukemia cell lines through the Wnt signaling pathway |
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