Triptolide blocks the STAT3 signaling pathway through induction of protein tyrosine phosphatase SHP-1 in multiple myeloma cells
Triptolide, an active component extracted from the medicinal plant Tripterygium wilfordii Hook F., has been used to treat various diseases, including lupus, cancer, rheumatoid arthritis and nephritic syndrome. The present study investigated the effects of triptolide on multiple myeloma using western...
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| Veröffentlicht in: | International journal of molecular medicine 2017-11, Vol.40 (5), p.1566-1572 |
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| description | Triptolide, an active component extracted from the medicinal plant Tripterygium wilfordii Hook F., has been used to treat various diseases, including lupus, cancer, rheumatoid arthritis and nephritic syndrome. The present study investigated the effects of triptolide on multiple myeloma using western blotting and an electrophoretic mobility shift assay. Triptolide was found to suppress the inducible and constitutive activation of signal transducer and activator of transcription 3 (STAT3), which is closely associated with inflammation and tumorigenesis. Triptolide also inhibited the DNA binding of STAT3. This correlated with the downregulation of Src kinase and Janus kinase 1 and 2, and with the upregulation of protein tyrosine phosphatase non-receptor type 6 (also known as SHP-1). In addition, trip-tolide downregulated the expression of the STAT3-regulated antiapoptotic (Bcl-xL and myeloid cell leukemia-1), proliferative (cyclin D1), and angiogenic (vascular endothelial growth factor) genes, suggesting that triptolide can induce apoptosis of tumor cells. These results suggest that triptolide may be a potential therapeutic anticancer agent for the prevention and treatment of multiple myeloma; thus further in-depth investigations into its efficacy and toxicity are warranted. |
| doi_str_mv | 10.3892/ijmm.2017.3122 |
| format | Article |
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The present study investigated the effects of triptolide on multiple myeloma using western blotting and an electrophoretic mobility shift assay. Triptolide was found to suppress the inducible and constitutive activation of signal transducer and activator of transcription 3 (STAT3), which is closely associated with inflammation and tumorigenesis. Triptolide also inhibited the DNA binding of STAT3. This correlated with the downregulation of Src kinase and Janus kinase 1 and 2, and with the upregulation of protein tyrosine phosphatase non-receptor type 6 (also known as SHP-1). In addition, trip-tolide downregulated the expression of the STAT3-regulated antiapoptotic (Bcl-xL and myeloid cell leukemia-1), proliferative (cyclin D1), and angiogenic (vascular endothelial growth factor) genes, suggesting that triptolide can induce apoptosis of tumor cells. These results suggest that triptolide may be a potential therapeutic anticancer agent for the prevention and treatment of multiple myeloma; thus further in-depth investigations into its efficacy and toxicity are warranted.</description><identifier>ISSN: 1107-3756</identifier><identifier>EISSN: 1791-244X</identifier><identifier>DOI: 10.3892/ijmm.2017.3122</identifier><identifier>PMID: 28901387</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>Angiogenesis ; Antibiotics ; Antineoplastic Agents, Alkylating - chemistry ; Antineoplastic Agents, Alkylating - pharmacology ; Apoptosis ; Autoimmune diseases ; Cancer therapies ; Care and treatment ; Cell Line, Tumor ; Cellular signal transduction ; Chinese medicine ; Cytokines ; Development and progression ; Disease ; Diterpenes - chemistry ; Diterpenes - pharmacology ; Dose-Response Relationship, Drug ; Enzyme Activation ; Epoxy compounds ; Epoxy Compounds - chemistry ; Epoxy Compounds - pharmacology ; Gene Expression Regulation, Neoplastic - drug effects ; Genetic aspects ; Growth factors ; Health aspects ; Humans ; Immunoglobulins ; Janus kinase ; Janus Kinase 1 - metabolism ; Janus Kinase 2 - metabolism ; Kinases ; Laboratories ; Multiple myeloma ; Multiple Myeloma - genetics ; Multiple Myeloma - metabolism ; Multiple Myeloma - pathology ; Phenanthrenes - chemistry ; Phenanthrenes - pharmacology ; Phosphatase ; Phosphorylation ; Protein Binding ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 - genetics ; Proteins ; SHP-1 ; signal transducer and activator of transcription 3 ; Signal Transduction - drug effects ; src-Family Kinases - metabolism ; STAT3 ; STAT3 Transcription Factor - metabolism ; Stem cells ; Studies ; Transcription factors ; triptolide</subject><ispartof>International journal of molecular medicine, 2017-11, Vol.40 (5), p.1566-1572</ispartof><rights>Copyright © 2017, Spandidos Publications</rights><rights>COPYRIGHT 2017 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-2fcb51895b8e0fa6afbbafc640460c8518439766529d7177d80fe6839768d66c3</citedby><cites>FETCH-LOGICAL-c463t-2fcb51895b8e0fa6afbbafc640460c8518439766529d7177d80fe6839768d66c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,5569,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28901387$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Ji-Hun</creatorcontrib><creatorcontrib>Park, Byoungduck</creatorcontrib><title>Triptolide blocks the STAT3 signaling pathway through induction of protein tyrosine phosphatase SHP-1 in multiple myeloma cells</title><title>International journal of molecular medicine</title><addtitle>Int J Mol Med</addtitle><description>Triptolide, an active component extracted from the medicinal plant Tripterygium wilfordii Hook F., has been used to treat various diseases, including lupus, cancer, rheumatoid arthritis and nephritic syndrome. The present study investigated the effects of triptolide on multiple myeloma using western blotting and an electrophoretic mobility shift assay. Triptolide was found to suppress the inducible and constitutive activation of signal transducer and activator of transcription 3 (STAT3), which is closely associated with inflammation and tumorigenesis. Triptolide also inhibited the DNA binding of STAT3. This correlated with the downregulation of Src kinase and Janus kinase 1 and 2, and with the upregulation of protein tyrosine phosphatase non-receptor type 6 (also known as SHP-1). In addition, trip-tolide downregulated the expression of the STAT3-regulated antiapoptotic (Bcl-xL and myeloid cell leukemia-1), proliferative (cyclin D1), and angiogenic (vascular endothelial growth factor) genes, suggesting that triptolide can induce apoptosis of tumor cells. These results suggest that triptolide may be a potential therapeutic anticancer agent for the prevention and treatment of multiple myeloma; thus further in-depth investigations into its efficacy and toxicity are warranted.</description><subject>Angiogenesis</subject><subject>Antibiotics</subject><subject>Antineoplastic Agents, Alkylating - chemistry</subject><subject>Antineoplastic Agents, Alkylating - pharmacology</subject><subject>Apoptosis</subject><subject>Autoimmune diseases</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Cell Line, Tumor</subject><subject>Cellular signal transduction</subject><subject>Chinese medicine</subject><subject>Cytokines</subject><subject>Development and progression</subject><subject>Disease</subject><subject>Diterpenes - chemistry</subject><subject>Diterpenes - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzyme Activation</subject><subject>Epoxy compounds</subject><subject>Epoxy Compounds - chemistry</subject><subject>Epoxy Compounds - pharmacology</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Genetic aspects</subject><subject>Growth factors</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Immunoglobulins</subject><subject>Janus kinase</subject><subject>Janus Kinase 1 - metabolism</subject><subject>Janus Kinase 2 - metabolism</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Multiple myeloma</subject><subject>Multiple Myeloma - genetics</subject><subject>Multiple Myeloma - metabolism</subject><subject>Multiple Myeloma - pathology</subject><subject>Phenanthrenes - chemistry</subject><subject>Phenanthrenes - pharmacology</subject><subject>Phosphatase</subject><subject>Phosphorylation</subject><subject>Protein Binding</subject><subject>Protein Tyrosine Phosphatase, Non-Receptor Type 6 - genetics</subject><subject>Proteins</subject><subject>SHP-1</subject><subject>signal transducer and activator of transcription 3</subject><subject>Signal Transduction - drug effects</subject><subject>src-Family Kinases - metabolism</subject><subject>STAT3</subject><subject>STAT3 Transcription Factor - metabolism</subject><subject>Stem cells</subject><subject>Studies</subject><subject>Transcription factors</subject><subject>triptolide</subject><issn>1107-3756</issn><issn>1791-244X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNptkcuLFDEQxhtR3HX16lECXrz0mEfn0cdhUVdYUHAEbyGdx3TGpNN20sic_NdNs-t6WeqQoupXH5X6muY1gjsievzen2LcYYj4jiCMnzSXiPeoxV3342nNEeQt4ZRdNC9yPkGIadeL580FFj1ERPDL5s9h8XNJwRsLhpD0zwzKaMG3w_5AQPbHSQU_HcGsyvhbnWtvSetxBH4yqy4-TSA5MC-pWD-Bcl5S9pMF85jyPKqiclW6-dqiyoO4huLnYEE825CiAtqGkF82z5wK2b66f6-a7x8_HK5v2tsvnz5f729b3TFSWuz0QJHo6SAsdIopNwzKadbBjkEtaqsjPWeM4t5wxLkR0FkmtpowjGly1by9063L_lptLvKU1qX-LkvU15MhxAj_Tx1VsNJPLpVF6eizlnuKCe8pxahSu0eoGsZGr9Nkna_1xwZ0PVBerJPz4qNazhJBudkoNxvlZqPcbKwDb-63XYdozQP-z7cKvLsD8qwm403KD8wm1XawhbRFlDHyF00dpgE</recordid><startdate>20171101</startdate><enddate>20171101</enddate><creator>Kim, Ji-Hun</creator><creator>Park, Byoungduck</creator><general>D.A. Spandidos</general><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20171101</creationdate><title>Triptolide blocks the STAT3 signaling pathway through induction of protein tyrosine phosphatase SHP-1 in multiple myeloma cells</title><author>Kim, Ji-Hun ; Park, Byoungduck</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c463t-2fcb51895b8e0fa6afbbafc640460c8518439766529d7177d80fe6839768d66c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Angiogenesis</topic><topic>Antibiotics</topic><topic>Antineoplastic Agents, Alkylating - chemistry</topic><topic>Antineoplastic Agents, Alkylating - pharmacology</topic><topic>Apoptosis</topic><topic>Autoimmune diseases</topic><topic>Cancer therapies</topic><topic>Care and treatment</topic><topic>Cell Line, Tumor</topic><topic>Cellular signal transduction</topic><topic>Chinese medicine</topic><topic>Cytokines</topic><topic>Development and progression</topic><topic>Disease</topic><topic>Diterpenes - chemistry</topic><topic>Diterpenes - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzyme Activation</topic><topic>Epoxy compounds</topic><topic>Epoxy Compounds - chemistry</topic><topic>Epoxy Compounds - pharmacology</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Genetic aspects</topic><topic>Growth factors</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Immunoglobulins</topic><topic>Janus kinase</topic><topic>Janus Kinase 1 - metabolism</topic><topic>Janus Kinase 2 - metabolism</topic><topic>Kinases</topic><topic>Laboratories</topic><topic>Multiple myeloma</topic><topic>Multiple Myeloma - genetics</topic><topic>Multiple Myeloma - metabolism</topic><topic>Multiple Myeloma - pathology</topic><topic>Phenanthrenes - chemistry</topic><topic>Phenanthrenes - pharmacology</topic><topic>Phosphatase</topic><topic>Phosphorylation</topic><topic>Protein Binding</topic><topic>Protein Tyrosine Phosphatase, Non-Receptor Type 6 - genetics</topic><topic>Proteins</topic><topic>SHP-1</topic><topic>signal transducer and activator of transcription 3</topic><topic>Signal Transduction - drug effects</topic><topic>src-Family Kinases - metabolism</topic><topic>STAT3</topic><topic>STAT3 Transcription Factor - metabolism</topic><topic>Stem cells</topic><topic>Studies</topic><topic>Transcription factors</topic><topic>triptolide</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Ji-Hun</creatorcontrib><creatorcontrib>Park, Byoungduck</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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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><jtitle>International journal of molecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Ji-Hun</au><au>Park, Byoungduck</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Triptolide blocks the STAT3 signaling pathway through induction of protein tyrosine phosphatase SHP-1 in multiple myeloma cells</atitle><jtitle>International journal of molecular medicine</jtitle><addtitle>Int J Mol Med</addtitle><date>2017-11-01</date><risdate>2017</risdate><volume>40</volume><issue>5</issue><spage>1566</spage><epage>1572</epage><pages>1566-1572</pages><issn>1107-3756</issn><eissn>1791-244X</eissn><abstract>Triptolide, an active component extracted from the medicinal plant Tripterygium wilfordii Hook F., has been used to treat various diseases, including lupus, cancer, rheumatoid arthritis and nephritic syndrome. The present study investigated the effects of triptolide on multiple myeloma using western blotting and an electrophoretic mobility shift assay. Triptolide was found to suppress the inducible and constitutive activation of signal transducer and activator of transcription 3 (STAT3), which is closely associated with inflammation and tumorigenesis. Triptolide also inhibited the DNA binding of STAT3. This correlated with the downregulation of Src kinase and Janus kinase 1 and 2, and with the upregulation of protein tyrosine phosphatase non-receptor type 6 (also known as SHP-1). In addition, trip-tolide downregulated the expression of the STAT3-regulated antiapoptotic (Bcl-xL and myeloid cell leukemia-1), proliferative (cyclin D1), and angiogenic (vascular endothelial growth factor) genes, suggesting that triptolide can induce apoptosis of tumor cells. These results suggest that triptolide may be a potential therapeutic anticancer agent for the prevention and treatment of multiple myeloma; thus further in-depth investigations into its efficacy and toxicity are warranted.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>28901387</pmid><doi>10.3892/ijmm.2017.3122</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | Spandidos Publications Journals; MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Angiogenesis Antibiotics Antineoplastic Agents, Alkylating - chemistry Antineoplastic Agents, Alkylating - pharmacology Apoptosis Autoimmune diseases Cancer therapies Care and treatment Cell Line, Tumor Cellular signal transduction Chinese medicine Cytokines Development and progression Disease Diterpenes - chemistry Diterpenes - pharmacology Dose-Response Relationship, Drug Enzyme Activation Epoxy compounds Epoxy Compounds - chemistry Epoxy Compounds - pharmacology Gene Expression Regulation, Neoplastic - drug effects Genetic aspects Growth factors Health aspects Humans Immunoglobulins Janus kinase Janus Kinase 1 - metabolism Janus Kinase 2 - metabolism Kinases Laboratories Multiple myeloma Multiple Myeloma - genetics Multiple Myeloma - metabolism Multiple Myeloma - pathology Phenanthrenes - chemistry Phenanthrenes - pharmacology Phosphatase Phosphorylation Protein Binding Protein Tyrosine Phosphatase, Non-Receptor Type 6 - genetics Proteins SHP-1 signal transducer and activator of transcription 3 Signal Transduction - drug effects src-Family Kinases - metabolism STAT3 STAT3 Transcription Factor - metabolism Stem cells Studies Transcription factors triptolide |
| title | Triptolide blocks the STAT3 signaling pathway through induction of protein tyrosine phosphatase SHP-1 in multiple myeloma cells |
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