Dual inhibition of histone deacetylases and phosphoinositide 3‐kinases: effects on Burkitt lymphoma cell growth and migration
The HDACi/PI3Ki combination suppresses BL cell proliferation and migration through alterations in PI3K signaling and HDAC function. Burkitt lymphoma is a highly aggressive non‐Hodgkin lymphoma that is characterized by MYC deregulation. Recently, the PI3K pathway has emerged as a cooperative prosurvi...
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| Veröffentlicht in: | Journal of leukocyte biology 2016-04, Vol.99 (4), p.569-578 |
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| container_title | Journal of leukocyte biology |
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| creator | Ferreira, Ana Carolina dos Santos de‐Freitas‐Junior, Julio Cesar Madureira Morgado‐Díaz, Jose Andres Ridley, Anne J. Klumb, Claudete Esteves |
| description | The HDACi/PI3Ki combination suppresses BL cell proliferation and migration through alterations in PI3K signaling and HDAC function.
Burkitt lymphoma is a highly aggressive non‐Hodgkin lymphoma that is characterized by MYC deregulation. Recently, the PI3K pathway has emerged as a cooperative prosurvival mechanism in Burkitt lymphoma. Despite the highly successful results of treatment that use high‐dose chemotherapy regimens in pediatric Burkitt lymphoma patients, the survival rate of pediatric patients with progressive or recurrent disease is low. PI3Ks are also known to regulate cell migration, and abnormal cell migration may contribute to cancer progression and dissemination in Burkitt lymphoma. Little is known about Burkitt lymphoma cell migration, but the cooperation between MYC and PI3K in Burkitt lymphoma pathogenesis suggests that a drug combination could be used to target the different steps involved in Burkitt lymphoma cell dissemination and disease progression. The aim of this study was to investigate the effects of the histone deacetylase inhibitor suberoylanilide hydroxamic acid combined with the PI3K inhibitor LY294002 on Burkitt lymphoma cell growth and migration. The combination enhanced the cell growth inhibition and cell‐cycle arrest induced by the PI3K inhibitor or histone deacetylase inhibitor individually. Moreover, histone deacetylase inhibitor/PI3K inhibitor cotreatment suppressed Burkitt lymphoma cell migration and decreased cell polarization, Akt and ERK1/2 phosphorylation, and leads to RhoB induction. In summary, the histone deacetylase inhibitor/PI3Ki combination inhibits cell proliferation and migration via alterations in PI3K signaling and histone deacetylase activity, which is involved in the acetylation of α‐tubulin and the regulation of RhoB expression. |
| doi_str_mv | 10.1189/jlb.2A0415-162R |
| format | Article |
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Burkitt lymphoma is a highly aggressive non‐Hodgkin lymphoma that is characterized by MYC deregulation. Recently, the PI3K pathway has emerged as a cooperative prosurvival mechanism in Burkitt lymphoma. Despite the highly successful results of treatment that use high‐dose chemotherapy regimens in pediatric Burkitt lymphoma patients, the survival rate of pediatric patients with progressive or recurrent disease is low. PI3Ks are also known to regulate cell migration, and abnormal cell migration may contribute to cancer progression and dissemination in Burkitt lymphoma. Little is known about Burkitt lymphoma cell migration, but the cooperation between MYC and PI3K in Burkitt lymphoma pathogenesis suggests that a drug combination could be used to target the different steps involved in Burkitt lymphoma cell dissemination and disease progression. The aim of this study was to investigate the effects of the histone deacetylase inhibitor suberoylanilide hydroxamic acid combined with the PI3K inhibitor LY294002 on Burkitt lymphoma cell growth and migration. The combination enhanced the cell growth inhibition and cell‐cycle arrest induced by the PI3K inhibitor or histone deacetylase inhibitor individually. Moreover, histone deacetylase inhibitor/PI3K inhibitor cotreatment suppressed Burkitt lymphoma cell migration and decreased cell polarization, Akt and ERK1/2 phosphorylation, and leads to RhoB induction. In summary, the histone deacetylase inhibitor/PI3Ki combination inhibits cell proliferation and migration via alterations in PI3K signaling and histone deacetylase activity, which is involved in the acetylation of α‐tubulin and the regulation of RhoB expression.</description><identifier>ISSN: 0741-5400</identifier><identifier>EISSN: 1938-3673</identifier><identifier>DOI: 10.1189/jlb.2A0415-162R</identifier><identifier>PMID: 26561567</identifier><language>eng</language><publisher>England</publisher><subject>Burkitt Lymphoma - enzymology ; Burkitt Lymphoma - pathology ; Cell Line, Tumor ; Cell Movement - drug effects ; Chromones - pharmacology ; Gene Expression Regulation, Neoplastic - drug effects ; histone deacetylase inhibitor ; Histone Deacetylase Inhibitors - pharmacology ; Histone Deacetylases - metabolism ; Humans ; MAP Kinase Signaling System - drug effects ; Mitogen-Activated Protein Kinase 1 - biosynthesis ; Mitogen-Activated Protein Kinase 3 - biosynthesis ; Morpholines - pharmacology ; non‐Hodgkin lymphoma ; phosphoinositide 3‐kinase inhibitor ; Phosphoinositide-3 Kinase Inhibitors ; Proto-Oncogene Proteins c-akt - biosynthesis ; Proto-Oncogene Proteins c-myc - biosynthesis ; Rho GTPase ; rhoB GTP-Binding Protein - biosynthesis</subject><ispartof>Journal of leukocyte biology, 2016-04, Vol.99 (4), p.569-578</ispartof><rights>2016 Society for Leukocyte Biology</rights><rights>Society for Leukocyte Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3839-29d4c4ec398e5593db6b8c6c5a2e5c8d0b4c97eb2fab35c97b751765554d62c83</citedby><cites>FETCH-LOGICAL-c3839-29d4c4ec398e5593db6b8c6c5a2e5c8d0b4c97eb2fab35c97b751765554d62c83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1189%2Fjlb.2A0415-162R$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1189%2Fjlb.2A0415-162R$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26561567$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ferreira, Ana Carolina dos Santos</creatorcontrib><creatorcontrib>de‐Freitas‐Junior, Julio Cesar Madureira</creatorcontrib><creatorcontrib>Morgado‐Díaz, Jose Andres</creatorcontrib><creatorcontrib>Ridley, Anne J.</creatorcontrib><creatorcontrib>Klumb, Claudete Esteves</creatorcontrib><title>Dual inhibition of histone deacetylases and phosphoinositide 3‐kinases: effects on Burkitt lymphoma cell growth and migration</title><title>Journal of leukocyte biology</title><addtitle>J Leukoc Biol</addtitle><description>The HDACi/PI3Ki combination suppresses BL cell proliferation and migration through alterations in PI3K signaling and HDAC function.
Burkitt lymphoma is a highly aggressive non‐Hodgkin lymphoma that is characterized by MYC deregulation. Recently, the PI3K pathway has emerged as a cooperative prosurvival mechanism in Burkitt lymphoma. Despite the highly successful results of treatment that use high‐dose chemotherapy regimens in pediatric Burkitt lymphoma patients, the survival rate of pediatric patients with progressive or recurrent disease is low. PI3Ks are also known to regulate cell migration, and abnormal cell migration may contribute to cancer progression and dissemination in Burkitt lymphoma. Little is known about Burkitt lymphoma cell migration, but the cooperation between MYC and PI3K in Burkitt lymphoma pathogenesis suggests that a drug combination could be used to target the different steps involved in Burkitt lymphoma cell dissemination and disease progression. The aim of this study was to investigate the effects of the histone deacetylase inhibitor suberoylanilide hydroxamic acid combined with the PI3K inhibitor LY294002 on Burkitt lymphoma cell growth and migration. The combination enhanced the cell growth inhibition and cell‐cycle arrest induced by the PI3K inhibitor or histone deacetylase inhibitor individually. Moreover, histone deacetylase inhibitor/PI3K inhibitor cotreatment suppressed Burkitt lymphoma cell migration and decreased cell polarization, Akt and ERK1/2 phosphorylation, and leads to RhoB induction. In summary, the histone deacetylase inhibitor/PI3Ki combination inhibits cell proliferation and migration via alterations in PI3K signaling and histone deacetylase activity, which is involved in the acetylation of α‐tubulin and the regulation of RhoB expression.</description><subject>Burkitt Lymphoma - enzymology</subject><subject>Burkitt Lymphoma - pathology</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Chromones - pharmacology</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>histone deacetylase inhibitor</subject><subject>Histone Deacetylase Inhibitors - pharmacology</subject><subject>Histone Deacetylases - metabolism</subject><subject>Humans</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Mitogen-Activated Protein Kinase 1 - biosynthesis</subject><subject>Mitogen-Activated Protein Kinase 3 - biosynthesis</subject><subject>Morpholines - pharmacology</subject><subject>non‐Hodgkin lymphoma</subject><subject>phosphoinositide 3‐kinase inhibitor</subject><subject>Phosphoinositide-3 Kinase Inhibitors</subject><subject>Proto-Oncogene Proteins c-akt - biosynthesis</subject><subject>Proto-Oncogene Proteins c-myc - biosynthesis</subject><subject>Rho GTPase</subject><subject>rhoB GTP-Binding Protein - biosynthesis</subject><issn>0741-5400</issn><issn>1938-3673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtOwzAQRS0EoqWwZof8A2n9iJ2EXcsbVUJCsI5sx2ncOkkVp6qygk_gG_kSHAJsWYxmFufekQ4A5xhNMY6T2drKKZmjELMAc_J8AMY4oXFAeUQPwRhFIQ5YiNAInDi3RghRwtExGBHOOGY8GoO3652w0FSFkaY1dQXrHBbGtXWlYaaF0m1nhdMOiiqD26J2fkxVOw9nGtLP94-NqXrgEuo816p10Jcsds3GtC20Xen5UkClrYWrpt63xXdTaVaN6P-dgqNcWKfPfvYEvN7evFzdB8unu4er-TJQNKZJQJIsVKFWNIk1YwnNJJex4ooJopmKMyRDlURaklxIyvwpI4YjzhgLM05UTCdgNvSqpnau0Xm6bUwpmi7FKO1Vpl5lOqhMe5U-cTEktjtZ6uyP_3XngXAA9sbq7r--9HG5QIwn9AvLO4PX</recordid><startdate>201604</startdate><enddate>201604</enddate><creator>Ferreira, Ana Carolina dos Santos</creator><creator>de‐Freitas‐Junior, Julio Cesar Madureira</creator><creator>Morgado‐Díaz, Jose Andres</creator><creator>Ridley, Anne J.</creator><creator>Klumb, Claudete Esteves</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></search><sort><creationdate>201604</creationdate><title>Dual inhibition of histone deacetylases and phosphoinositide 3‐kinases: effects on Burkitt lymphoma cell growth and migration</title><author>Ferreira, Ana Carolina dos Santos ; de‐Freitas‐Junior, Julio Cesar Madureira ; Morgado‐Díaz, Jose Andres ; Ridley, Anne J. ; Klumb, Claudete Esteves</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3839-29d4c4ec398e5593db6b8c6c5a2e5c8d0b4c97eb2fab35c97b751765554d62c83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Burkitt Lymphoma - enzymology</topic><topic>Burkitt Lymphoma - pathology</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - drug effects</topic><topic>Chromones - pharmacology</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>histone deacetylase inhibitor</topic><topic>Histone Deacetylase Inhibitors - pharmacology</topic><topic>Histone Deacetylases - metabolism</topic><topic>Humans</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Mitogen-Activated Protein Kinase 1 - biosynthesis</topic><topic>Mitogen-Activated Protein Kinase 3 - biosynthesis</topic><topic>Morpholines - pharmacology</topic><topic>non‐Hodgkin lymphoma</topic><topic>phosphoinositide 3‐kinase inhibitor</topic><topic>Phosphoinositide-3 Kinase Inhibitors</topic><topic>Proto-Oncogene Proteins c-akt - biosynthesis</topic><topic>Proto-Oncogene Proteins c-myc - biosynthesis</topic><topic>Rho GTPase</topic><topic>rhoB GTP-Binding Protein - biosynthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ferreira, Ana Carolina dos Santos</creatorcontrib><creatorcontrib>de‐Freitas‐Junior, Julio Cesar Madureira</creatorcontrib><creatorcontrib>Morgado‐Díaz, Jose Andres</creatorcontrib><creatorcontrib>Ridley, Anne J.</creatorcontrib><creatorcontrib>Klumb, Claudete Esteves</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of leukocyte biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ferreira, Ana Carolina dos Santos</au><au>de‐Freitas‐Junior, Julio Cesar Madureira</au><au>Morgado‐Díaz, Jose Andres</au><au>Ridley, Anne J.</au><au>Klumb, Claudete Esteves</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dual inhibition of histone deacetylases and phosphoinositide 3‐kinases: effects on Burkitt lymphoma cell growth and migration</atitle><jtitle>Journal of leukocyte biology</jtitle><addtitle>J Leukoc Biol</addtitle><date>2016-04</date><risdate>2016</risdate><volume>99</volume><issue>4</issue><spage>569</spage><epage>578</epage><pages>569-578</pages><issn>0741-5400</issn><eissn>1938-3673</eissn><abstract>The HDACi/PI3Ki combination suppresses BL cell proliferation and migration through alterations in PI3K signaling and HDAC function.
Burkitt lymphoma is a highly aggressive non‐Hodgkin lymphoma that is characterized by MYC deregulation. Recently, the PI3K pathway has emerged as a cooperative prosurvival mechanism in Burkitt lymphoma. Despite the highly successful results of treatment that use high‐dose chemotherapy regimens in pediatric Burkitt lymphoma patients, the survival rate of pediatric patients with progressive or recurrent disease is low. PI3Ks are also known to regulate cell migration, and abnormal cell migration may contribute to cancer progression and dissemination in Burkitt lymphoma. Little is known about Burkitt lymphoma cell migration, but the cooperation between MYC and PI3K in Burkitt lymphoma pathogenesis suggests that a drug combination could be used to target the different steps involved in Burkitt lymphoma cell dissemination and disease progression. The aim of this study was to investigate the effects of the histone deacetylase inhibitor suberoylanilide hydroxamic acid combined with the PI3K inhibitor LY294002 on Burkitt lymphoma cell growth and migration. The combination enhanced the cell growth inhibition and cell‐cycle arrest induced by the PI3K inhibitor or histone deacetylase inhibitor individually. Moreover, histone deacetylase inhibitor/PI3K inhibitor cotreatment suppressed Burkitt lymphoma cell migration and decreased cell polarization, Akt and ERK1/2 phosphorylation, and leads to RhoB induction. In summary, the histone deacetylase inhibitor/PI3Ki combination inhibits cell proliferation and migration via alterations in PI3K signaling and histone deacetylase activity, which is involved in the acetylation of α‐tubulin and the regulation of RhoB expression.</abstract><cop>England</cop><pmid>26561567</pmid><doi>10.1189/jlb.2A0415-162R</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0741-5400 |
| ispartof | Journal of leukocyte biology, 2016-04, Vol.99 (4), p.569-578 |
| issn | 0741-5400 1938-3673 |
| language | eng |
| recordid | cdi_crossref_primary_10_1189_jlb_2A0415_162R |
| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Burkitt Lymphoma - enzymology Burkitt Lymphoma - pathology Cell Line, Tumor Cell Movement - drug effects Chromones - pharmacology Gene Expression Regulation, Neoplastic - drug effects histone deacetylase inhibitor Histone Deacetylase Inhibitors - pharmacology Histone Deacetylases - metabolism Humans MAP Kinase Signaling System - drug effects Mitogen-Activated Protein Kinase 1 - biosynthesis Mitogen-Activated Protein Kinase 3 - biosynthesis Morpholines - pharmacology non‐Hodgkin lymphoma phosphoinositide 3‐kinase inhibitor Phosphoinositide-3 Kinase Inhibitors Proto-Oncogene Proteins c-akt - biosynthesis Proto-Oncogene Proteins c-myc - biosynthesis Rho GTPase rhoB GTP-Binding Protein - biosynthesis |
| title | Dual inhibition of histone deacetylases and phosphoinositide 3‐kinases: effects on Burkitt lymphoma cell growth and migration |
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