MK886 inhibits the proliferation of HL-60 leukemia cells by suppressing the expression of mPGES-1 and reducing prostaglandin E2 synthesis
Microsomal prostaglandin E synthase-1 (mPGES-1), an inducible enzyme that specifically catalyzes the conversion of prostaglandin H2 (PGH2) to prostaglandin E2 (PGE2), has been reported to be over-expressed in a variety of solid tumor cells and tissues, but not in normal tissues. Its association with...
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| Veröffentlicht in: | International journal of hematology 2011-11, Vol.94 (5), p.472-478 |
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| container_title | International journal of hematology |
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| creator | Li, YiQing Yin, SongMei Nie, DaNian Xie, ShuangFeng Ma, LiPing Wang, XiuJu Wu, YuDan Xiao, Jie |
| description | Microsomal prostaglandin E synthase-1 (mPGES-1), an inducible enzyme that specifically catalyzes the conversion of prostaglandin H2 (PGH2) to prostaglandin E2 (PGE2), has been reported to be over-expressed in a variety of solid tumor cells and tissues, but not in normal tissues. Its association with leukemia, however, has not been fully investigated. Our study revealed, for the first time, that mPGES-1 is over-expressed in human acute myeloid leukemia HL-60 cells. Cytotoxicity assays and flow cytometry showed that MK886, an inhibitor of mPGES-1, inhibits proliferation of HL-60 cells and induces apoptosis in a dose- and time-dependent manner, which may result from down-regulation of mPGES-1 expression and PGE2 synthesis. Evaluation of mediators of apoptotic signaling revealed up-regulation of BAX expression and caspase-3 activity, as well as significant decreases in Bcl2 and P-Akt. We conclude that MK886 reduces the viability of leukemia HL-60 cells by reducing mPGES-1 expression and PGE2 synthesis in a dose-dependent manner, which strongly suggests that mPGES-1 inhibitors should be considered as promising candidates for leukemia treatment. |
| doi_str_mv | 10.1007/s12185-011-0954-0 |
| format | Article |
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Its association with leukemia, however, has not been fully investigated. Our study revealed, for the first time, that mPGES-1 is over-expressed in human acute myeloid leukemia HL-60 cells. Cytotoxicity assays and flow cytometry showed that MK886, an inhibitor of mPGES-1, inhibits proliferation of HL-60 cells and induces apoptosis in a dose- and time-dependent manner, which may result from down-regulation of mPGES-1 expression and PGE2 synthesis. Evaluation of mediators of apoptotic signaling revealed up-regulation of BAX expression and caspase-3 activity, as well as significant decreases in Bcl2 and P-Akt. We conclude that MK886 reduces the viability of leukemia HL-60 cells by reducing mPGES-1 expression and PGE2 synthesis in a dose-dependent manner, which strongly suggests that mPGES-1 inhibitors should be considered as promising candidates for leukemia treatment.</description><identifier>ISSN: 0925-5710</identifier><identifier>EISSN: 1865-3774</identifier><identifier>DOI: 10.1007/s12185-011-0954-0</identifier><identifier>PMID: 22038016</identifier><language>eng</language><publisher>Japan: Springer Japan</publisher><subject>Biological and medical sciences ; Cell Proliferation - drug effects ; Depression, Chemical ; Dinoprostone - biosynthesis ; Dose-Response Relationship, Drug ; Down-Regulation - drug effects ; Gene Expression Regulation, Enzymologic - drug effects ; Hematologic and hematopoietic diseases ; Hematology ; HL-60 Cells ; Humans ; Indoles - pharmacology ; Intramolecular Oxidoreductases - antagonists & inhibitors ; Intramolecular Oxidoreductases - metabolism ; Leukemia, Myeloid, Acute - enzymology ; Leukemia, Myeloid, Acute - metabolism ; Leukemia, Myeloid, Acute - pathology ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Lipoxygenase Inhibitors - pharmacology ; Medical sciences ; Medicine ; Medicine & Public Health ; Molecular Targeted Therapy ; Oncology ; Original Article ; Prostaglandin-E Synthases ; Time Factors ; Tumor Cells, Cultured</subject><ispartof>International journal of hematology, 2011-11, Vol.94 (5), p.472-478</ispartof><rights>The Japanese Society of Hematology 2011</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-bd2722444d03c9708444895386b69341c7a9a6d1ffb7f6229318f40450469d533</citedby><cites>FETCH-LOGICAL-c453t-bd2722444d03c9708444895386b69341c7a9a6d1ffb7f6229318f40450469d533</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/s12185-011-0954-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12185-011-0954-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51298</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25589989$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22038016$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, YiQing</creatorcontrib><creatorcontrib>Yin, SongMei</creatorcontrib><creatorcontrib>Nie, DaNian</creatorcontrib><creatorcontrib>Xie, ShuangFeng</creatorcontrib><creatorcontrib>Ma, LiPing</creatorcontrib><creatorcontrib>Wang, XiuJu</creatorcontrib><creatorcontrib>Wu, YuDan</creatorcontrib><creatorcontrib>Xiao, Jie</creatorcontrib><title>MK886 inhibits the proliferation of HL-60 leukemia cells by suppressing the expression of mPGES-1 and reducing prostaglandin E2 synthesis</title><title>International journal of hematology</title><addtitle>Int J Hematol</addtitle><addtitle>Int J Hematol</addtitle><description>Microsomal prostaglandin E synthase-1 (mPGES-1), an inducible enzyme that specifically catalyzes the conversion of prostaglandin H2 (PGH2) to prostaglandin E2 (PGE2), has been reported to be over-expressed in a variety of solid tumor cells and tissues, but not in normal tissues. Its association with leukemia, however, has not been fully investigated. Our study revealed, for the first time, that mPGES-1 is over-expressed in human acute myeloid leukemia HL-60 cells. Cytotoxicity assays and flow cytometry showed that MK886, an inhibitor of mPGES-1, inhibits proliferation of HL-60 cells and induces apoptosis in a dose- and time-dependent manner, which may result from down-regulation of mPGES-1 expression and PGE2 synthesis. Evaluation of mediators of apoptotic signaling revealed up-regulation of BAX expression and caspase-3 activity, as well as significant decreases in Bcl2 and P-Akt. We conclude that MK886 reduces the viability of leukemia HL-60 cells by reducing mPGES-1 expression and PGE2 synthesis in a dose-dependent manner, which strongly suggests that mPGES-1 inhibitors should be considered as promising candidates for leukemia treatment.</description><subject>Biological and medical sciences</subject><subject>Cell Proliferation - drug effects</subject><subject>Depression, Chemical</subject><subject>Dinoprostone - biosynthesis</subject><subject>Dose-Response Relationship, Drug</subject><subject>Down-Regulation - drug effects</subject><subject>Gene Expression Regulation, Enzymologic - drug effects</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematology</subject><subject>HL-60 Cells</subject><subject>Humans</subject><subject>Indoles - pharmacology</subject><subject>Intramolecular Oxidoreductases - antagonists & inhibitors</subject><subject>Intramolecular Oxidoreductases - metabolism</subject><subject>Leukemia, Myeloid, Acute - enzymology</subject><subject>Leukemia, Myeloid, Acute - metabolism</subject><subject>Leukemia, Myeloid, Acute - pathology</subject><subject>Leukemias. 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Myelofibrosis</subject><subject>Lipoxygenase Inhibitors - pharmacology</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Molecular Targeted Therapy</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Prostaglandin-E Synthases</subject><subject>Time Factors</subject><subject>Tumor Cells, Cultured</subject><issn>0925-5710</issn><issn>1865-3774</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kM2OFCEUhYnROO3oA7gxxMQlevmHpZm0M8Y2mqhrQlVBD2M13UJVYj-Cby1ttc7KFXD5zj0nB6HnFF5TAP2mUkaNJEApASsFgQdoRY2ShGstHqIVWCaJ1BQu0JNa7wCoBqEfowvGgBugaoV-ffxgjMIp36YuTRVPtwEfyn5MMRQ_pX3G-4hvNkQBHsP8PeySx30Yx4q7I67z4VBCrSlv_wjDz-W5qHafr9dfCMU-D7iEYe5PWNtdJ78d2zBlvGa4HnOT1lSfokfRjzU8O5-X6Nu79derG7L5dP3-6u2G9ELyiXQD04wJIQbgvdVg2tVYyY3qlOWC9tpbrwYaY6ejYsxyaqIAIUEoO0jOL9HLZW-L8mMOdXJ3-7nkZuksCK60EbZBdIH6lreWEN2hpJ0vR0fBnbp3S_eude9O3TtomhfnxXO3C8M_xd-yG_DqDPja-zEWn_tU7zkpjbXmZM4WrravvA3lPuH_3X8DRh-aRA</recordid><startdate>20111101</startdate><enddate>20111101</enddate><creator>Li, YiQing</creator><creator>Yin, SongMei</creator><creator>Nie, DaNian</creator><creator>Xie, ShuangFeng</creator><creator>Ma, LiPing</creator><creator>Wang, XiuJu</creator><creator>Wu, YuDan</creator><creator>Xiao, Jie</creator><general>Springer Japan</general><general>Springer</general><general>Springer Nature B.V</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>3V.</scope><scope>7RV</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20111101</creationdate><title>MK886 inhibits the proliferation of HL-60 leukemia cells by suppressing the expression of mPGES-1 and reducing prostaglandin E2 synthesis</title><author>Li, YiQing ; Yin, SongMei ; Nie, DaNian ; Xie, ShuangFeng ; Ma, LiPing ; Wang, XiuJu ; Wu, YuDan ; Xiao, Jie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c453t-bd2722444d03c9708444895386b69341c7a9a6d1ffb7f6229318f40450469d533</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Biological and medical sciences</topic><topic>Cell Proliferation - drug effects</topic><topic>Depression, Chemical</topic><topic>Dinoprostone - biosynthesis</topic><topic>Dose-Response Relationship, Drug</topic><topic>Down-Regulation - drug effects</topic><topic>Gene Expression Regulation, Enzymologic - drug effects</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hematology</topic><topic>HL-60 Cells</topic><topic>Humans</topic><topic>Indoles - pharmacology</topic><topic>Intramolecular Oxidoreductases - antagonists & inhibitors</topic><topic>Intramolecular Oxidoreductases - metabolism</topic><topic>Leukemia, Myeloid, Acute - enzymology</topic><topic>Leukemia, Myeloid, Acute - metabolism</topic><topic>Leukemia, Myeloid, Acute - pathology</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. 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Its association with leukemia, however, has not been fully investigated. Our study revealed, for the first time, that mPGES-1 is over-expressed in human acute myeloid leukemia HL-60 cells. Cytotoxicity assays and flow cytometry showed that MK886, an inhibitor of mPGES-1, inhibits proliferation of HL-60 cells and induces apoptosis in a dose- and time-dependent manner, which may result from down-regulation of mPGES-1 expression and PGE2 synthesis. Evaluation of mediators of apoptotic signaling revealed up-regulation of BAX expression and caspase-3 activity, as well as significant decreases in Bcl2 and P-Akt. We conclude that MK886 reduces the viability of leukemia HL-60 cells by reducing mPGES-1 expression and PGE2 synthesis in a dose-dependent manner, which strongly suggests that mPGES-1 inhibitors should be considered as promising candidates for leukemia treatment.</abstract><cop>Japan</cop><pub>Springer Japan</pub><pmid>22038016</pmid><doi>10.1007/s12185-011-0954-0</doi><tpages>7</tpages></addata></record> |
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| subjects | Biological and medical sciences Cell Proliferation - drug effects Depression, Chemical Dinoprostone - biosynthesis Dose-Response Relationship, Drug Down-Regulation - drug effects Gene Expression Regulation, Enzymologic - drug effects Hematologic and hematopoietic diseases Hematology HL-60 Cells Humans Indoles - pharmacology Intramolecular Oxidoreductases - antagonists & inhibitors Intramolecular Oxidoreductases - metabolism Leukemia, Myeloid, Acute - enzymology Leukemia, Myeloid, Acute - metabolism Leukemia, Myeloid, Acute - pathology Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Lipoxygenase Inhibitors - pharmacology Medical sciences Medicine Medicine & Public Health Molecular Targeted Therapy Oncology Original Article Prostaglandin-E Synthases Time Factors Tumor Cells, Cultured |
| title | MK886 inhibits the proliferation of HL-60 leukemia cells by suppressing the expression of mPGES-1 and reducing prostaglandin E2 synthesis |
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