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Scoparone exerts anti-tumor activity against DU145 prostate cancer cells via inhibition of STAT3 activity
Scoparone, a natural compound isolated from Artemisia capillaris, has been used in Chinese herbal medicine to treat neonatal jaundice. Signal transducer and activator of transcription 3 (STAT3) contributes to the growth and survival of many human tumors. This study was undertaken to investigate the...
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| Published in: | PloS one 2013-11, Vol.8 (11), p.e80391 |
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| cited_by | cdi_FETCH-LOGICAL-c758t-50841287518898b51668e4f12625266fe0c555e59a99284a76299fce4e7b2013 |
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| container_issue | 11 |
| container_start_page | e80391 |
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| creator | Kim, Jeong-Kook Kim, Joon-Young Kim, Han-Jong Park, Keun-Gyu Harris, Robert A Cho, Won-Jea Lee, Jae-Tae Lee, In-Kyu |
| description | Scoparone, a natural compound isolated from Artemisia capillaris, has been used in Chinese herbal medicine to treat neonatal jaundice. Signal transducer and activator of transcription 3 (STAT3) contributes to the growth and survival of many human tumors. This study was undertaken to investigate the anti-tumor activity of scoparone against DU145 prostate cancer cells and to determine whether its effects are mediated by inhibition of STAT3 activity. Scoparone inhibited proliferation of DU145 cells via cell cycle arrest in G1 phase. Transient transfection assays showed that scoparone repressed both constitutive and IL-6-induced transcriptional activity of STAT3. Western blot and quantitative real-time PCR analyses demonstrated that scoparone suppressed the transcription of STAT3 target genes such as cyclin D1, c-Myc, survivin, Bcl-2, and Socs3. Consistent with this, scoparone decreased phosphorylation and nuclear accumulation of STAT3, but did not reduce phosphorylation of janus kinase 2 (JAK2) or Src, the major upstream kinases responsible for STAT3 activation. Moreover, transcriptional activity of a constitutively active mutant of STAT3 (STAT3C) was inhibited by scoparone, but not by AG490, a JAK2 inhibitor. Furthermore, scoparone treatment suppressed anchorage-independent growth in soft agar and tumor growth of DU145 xenografts in nude mice, concomitant with a reduction in STAT3 phosphorylation. Computational modeling suggested that scoparone might bind the SH2 domain of STAT3. Our findings suggest that scoparone elicits an anti-tumor effect against DU145 prostate cancer cells in part through inhibition of STAT3 activity. |
| doi_str_mv | 10.1371/journal.pone.0080391 |
| format | article |
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Signal transducer and activator of transcription 3 (STAT3) contributes to the growth and survival of many human tumors. This study was undertaken to investigate the anti-tumor activity of scoparone against DU145 prostate cancer cells and to determine whether its effects are mediated by inhibition of STAT3 activity. Scoparone inhibited proliferation of DU145 cells via cell cycle arrest in G1 phase. Transient transfection assays showed that scoparone repressed both constitutive and IL-6-induced transcriptional activity of STAT3. Western blot and quantitative real-time PCR analyses demonstrated that scoparone suppressed the transcription of STAT3 target genes such as cyclin D1, c-Myc, survivin, Bcl-2, and Socs3. Consistent with this, scoparone decreased phosphorylation and nuclear accumulation of STAT3, but did not reduce phosphorylation of janus kinase 2 (JAK2) or Src, the major upstream kinases responsible for STAT3 activation. Moreover, transcriptional activity of a constitutively active mutant of STAT3 (STAT3C) was inhibited by scoparone, but not by AG490, a JAK2 inhibitor. Furthermore, scoparone treatment suppressed anchorage-independent growth in soft agar and tumor growth of DU145 xenografts in nude mice, concomitant with a reduction in STAT3 phosphorylation. Computational modeling suggested that scoparone might bind the SH2 domain of STAT3. Our findings suggest that scoparone elicits an anti-tumor effect against DU145 prostate cancer cells in part through inhibition of STAT3 activity.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0080391</identifier><identifier>PMID: 24260381</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Agar ; Aging ; Androgens ; Animals ; Antibiotics ; Anticancer properties ; Antineoplastic Agents - pharmacology ; Antitumor agents ; Apoptosis ; Artemisia - chemistry ; Bcl-2 protein ; Breast cancer ; c-Myc protein ; Cancer ; Cancer cells ; Cancer prevention ; Cancer research ; Cancer therapies ; Cell cycle ; Cell Cycle Checkpoints - drug effects ; Cell Line, Tumor ; Cell proliferation ; Cell Proliferation - drug effects ; Computer applications ; Coumarins - pharmacology ; Cyclin D1 ; Cyclin D1 - metabolism ; Cytokines ; Epidermal growth factor ; G1 phase ; G1 Phase - drug effects ; HCT116 Cells ; HeLa Cells ; Hep G2 Cells ; Herbal medicine ; HT29 Cells ; Humans ; Inhibition ; Inhibitor of Apoptosis Proteins - metabolism ; Interleukin 6 ; Interleukin-6 - metabolism ; Internal medicine ; Janus kinase ; Janus kinase 2 ; Janus Kinase 2 - metabolism ; Jaundice ; Kinases ; Male ; MCF-7 Cells ; Medicine ; Metabolism ; Metastasis ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mouse devices ; Myc protein ; Natural products ; Neonates ; Phosphorylation ; Phosphorylation - drug effects ; Prostate cancer ; Prostatic Neoplasms - drug therapy ; Prostatic Neoplasms - metabolism ; Proteins ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Proto-Oncogene Proteins c-myc - metabolism ; Rodents ; Signal Transduction - drug effects ; Stat3 protein ; STAT3 Transcription Factor - antagonists & inhibitors ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins - metabolism ; Survivin ; Transcription (Genetics) ; Transcription activation ; Transcription, Genetic - drug effects ; Transfection ; Tumors ; Xenografts ; Xenotransplantation</subject><ispartof>PloS one, 2013-11, Vol.8 (11), p.e80391</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Kim et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/3.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Kim et al 2013 Kim et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-50841287518898b51668e4f12625266fe0c555e59a99284a76299fce4e7b2013</citedby><cites>FETCH-LOGICAL-c758t-50841287518898b51668e4f12625266fe0c555e59a99284a76299fce4e7b2013</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1458745582/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1458745582?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,315,733,786,790,891,25783,27957,27958,37047,44625,53827,53829,75483</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24260381$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Muders, Michael</contributor><creatorcontrib>Kim, Jeong-Kook</creatorcontrib><creatorcontrib>Kim, Joon-Young</creatorcontrib><creatorcontrib>Kim, Han-Jong</creatorcontrib><creatorcontrib>Park, Keun-Gyu</creatorcontrib><creatorcontrib>Harris, Robert A</creatorcontrib><creatorcontrib>Cho, Won-Jea</creatorcontrib><creatorcontrib>Lee, Jae-Tae</creatorcontrib><creatorcontrib>Lee, In-Kyu</creatorcontrib><title>Scoparone exerts anti-tumor activity against DU145 prostate cancer cells via inhibition of STAT3 activity</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Scoparone, a natural compound isolated from Artemisia capillaris, has been used in Chinese herbal medicine to treat neonatal jaundice. Signal transducer and activator of transcription 3 (STAT3) contributes to the growth and survival of many human tumors. This study was undertaken to investigate the anti-tumor activity of scoparone against DU145 prostate cancer cells and to determine whether its effects are mediated by inhibition of STAT3 activity. Scoparone inhibited proliferation of DU145 cells via cell cycle arrest in G1 phase. Transient transfection assays showed that scoparone repressed both constitutive and IL-6-induced transcriptional activity of STAT3. Western blot and quantitative real-time PCR analyses demonstrated that scoparone suppressed the transcription of STAT3 target genes such as cyclin D1, c-Myc, survivin, Bcl-2, and Socs3. Consistent with this, scoparone decreased phosphorylation and nuclear accumulation of STAT3, but did not reduce phosphorylation of janus kinase 2 (JAK2) or Src, the major upstream kinases responsible for STAT3 activation. Moreover, transcriptional activity of a constitutively active mutant of STAT3 (STAT3C) was inhibited by scoparone, but not by AG490, a JAK2 inhibitor. Furthermore, scoparone treatment suppressed anchorage-independent growth in soft agar and tumor growth of DU145 xenografts in nude mice, concomitant with a reduction in STAT3 phosphorylation. Computational modeling suggested that scoparone might bind the SH2 domain of STAT3. Our findings suggest that scoparone elicits an anti-tumor effect against DU145 prostate cancer cells in part through inhibition of STAT3 activity.</description><subject>Agar</subject><subject>Aging</subject><subject>Androgens</subject><subject>Animals</subject><subject>Antibiotics</subject><subject>Anticancer properties</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antitumor agents</subject><subject>Apoptosis</subject><subject>Artemisia - chemistry</subject><subject>Bcl-2 protein</subject><subject>Breast cancer</subject><subject>c-Myc protein</subject><subject>Cancer</subject><subject>Cancer cells</subject><subject>Cancer prevention</subject><subject>Cancer research</subject><subject>Cancer therapies</subject><subject>Cell cycle</subject><subject>Cell Cycle Checkpoints - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Computer applications</subject><subject>Coumarins - pharmacology</subject><subject>Cyclin D1</subject><subject>Cyclin D1 - metabolism</subject><subject>Cytokines</subject><subject>Epidermal growth factor</subject><subject>G1 phase</subject><subject>G1 Phase - drug effects</subject><subject>HCT116 Cells</subject><subject>HeLa Cells</subject><subject>Hep G2 Cells</subject><subject>Herbal medicine</subject><subject>HT29 Cells</subject><subject>Humans</subject><subject>Inhibition</subject><subject>Inhibitor of Apoptosis Proteins - metabolism</subject><subject>Interleukin 6</subject><subject>Interleukin-6 - metabolism</subject><subject>Internal medicine</subject><subject>Janus kinase</subject><subject>Janus kinase 2</subject><subject>Janus Kinase 2 - metabolism</subject><subject>Jaundice</subject><subject>Kinases</subject><subject>Male</subject><subject>MCF-7 Cells</subject><subject>Medicine</subject><subject>Metabolism</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Mouse devices</subject><subject>Myc protein</subject><subject>Natural products</subject><subject>Neonates</subject><subject>Phosphorylation</subject><subject>Phosphorylation - drug effects</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms - drug therapy</subject><subject>Prostatic Neoplasms - metabolism</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Proto-Oncogene Proteins c-myc - metabolism</subject><subject>Rodents</subject><subject>Signal Transduction - drug effects</subject><subject>Stat3 protein</subject><subject>STAT3 Transcription Factor - antagonists & inhibitors</subject><subject>Suppressor of Cytokine Signaling 3 Protein</subject><subject>Suppressor of Cytokine Signaling Proteins - metabolism</subject><subject>Survivin</subject><subject>Transcription (Genetics)</subject><subject>Transcription activation</subject><subject>Transcription, Genetic - drug effects</subject><subject>Transfection</subject><subject>Tumors</subject><subject>Xenografts</subject><subject>Xenotransplantation</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl-LEzEUxQdR3HX1G4gGBMGH1iSTZO68CGX9V1hYsNXXkEkzbcp00k0yZffbm7GzpQMKkoeEm989uZycLHtN8JTkBfm4dZ1vVTPdu9ZMMQacl-RJdknKnE4ExfnTs_NF9iKELcY8ByGeZxeUUYFzIJeZXWi3Vz5pIHNvfAxItdFOYrdzHikd7cHGB6TWyrYhos8_CeNo712IKhqkVauNR9o0TUAHq5BtN7ay0boWuRotlrNlfhJ5mT2rVRPMq2G_ypZfvyyvv09ubr_Nr2c3E11wiBOOgREKBScAJVScCAGG1YQKyqkQtcGac254qcqSAlOFoGVZa8NMUVFM8qvs7VF237ggB5OCTHNDwTgHmoj5kVg5tZV7b3fKP0inrPxTcH4tlY9WN0Zqo6DWVclIXTABuiI5QFUwbYBpWEHS-jS81lU7s9KmjV41I9HxTWs3cu0OMgdaAhdJ4N0g4N1dZ0L8x8gDtVZpKtvWLonpnQ1azlgBvTdlP8z0L1RaK7OzOn1xbVN91PBh1JCYaO7jWnUhyPnix_-zt7_G7PszdmNUEzfBNV0fjDAG2RHUKVLBm_rkHMGyT_mjG7JPuRxSntrenLt-anqMdf4bHGX2ow</recordid><startdate>20131115</startdate><enddate>20131115</enddate><creator>Kim, Jeong-Kook</creator><creator>Kim, Joon-Young</creator><creator>Kim, Han-Jong</creator><creator>Park, Keun-Gyu</creator><creator>Harris, Robert A</creator><creator>Cho, Won-Jea</creator><creator>Lee, Jae-Tae</creator><creator>Lee, In-Kyu</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20131115</creationdate><title>Scoparone exerts anti-tumor activity against DU145 prostate cancer cells via inhibition of STAT3 activity</title><author>Kim, Jeong-Kook ; Kim, Joon-Young ; Kim, Han-Jong ; Park, Keun-Gyu ; Harris, Robert A ; Cho, Won-Jea ; Lee, Jae-Tae ; Lee, In-Kyu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-50841287518898b51668e4f12625266fe0c555e59a99284a76299fce4e7b2013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Agar</topic><topic>Aging</topic><topic>Androgens</topic><topic>Animals</topic><topic>Antibiotics</topic><topic>Anticancer properties</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antitumor agents</topic><topic>Apoptosis</topic><topic>Artemisia - chemistry</topic><topic>Bcl-2 protein</topic><topic>Breast cancer</topic><topic>c-Myc protein</topic><topic>Cancer</topic><topic>Cancer cells</topic><topic>Cancer prevention</topic><topic>Cancer research</topic><topic>Cancer therapies</topic><topic>Cell cycle</topic><topic>Cell Cycle Checkpoints - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>Computer applications</topic><topic>Coumarins - pharmacology</topic><topic>Cyclin D1</topic><topic>Cyclin D1 - metabolism</topic><topic>Cytokines</topic><topic>Epidermal growth factor</topic><topic>G1 phase</topic><topic>G1 Phase - drug effects</topic><topic>HCT116 Cells</topic><topic>HeLa Cells</topic><topic>Hep G2 Cells</topic><topic>Herbal medicine</topic><topic>HT29 Cells</topic><topic>Humans</topic><topic>Inhibition</topic><topic>Inhibitor of Apoptosis Proteins - metabolism</topic><topic>Interleukin 6</topic><topic>Interleukin-6 - metabolism</topic><topic>Internal medicine</topic><topic>Janus kinase</topic><topic>Janus kinase 2</topic><topic>Janus Kinase 2 - metabolism</topic><topic>Jaundice</topic><topic>Kinases</topic><topic>Male</topic><topic>MCF-7 Cells</topic><topic>Medicine</topic><topic>Metabolism</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Mouse devices</topic><topic>Myc protein</topic><topic>Natural products</topic><topic>Neonates</topic><topic>Phosphorylation</topic><topic>Phosphorylation - drug effects</topic><topic>Prostate cancer</topic><topic>Prostatic Neoplasms - drug therapy</topic><topic>Prostatic Neoplasms - metabolism</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><topic>Proto-Oncogene Proteins c-myc - metabolism</topic><topic>Rodents</topic><topic>Signal Transduction - drug effects</topic><topic>Stat3 protein</topic><topic>STAT3 Transcription Factor - antagonists & inhibitors</topic><topic>Suppressor of Cytokine Signaling 3 Protein</topic><topic>Suppressor of Cytokine Signaling Proteins - metabolism</topic><topic>Survivin</topic><topic>Transcription (Genetics)</topic><topic>Transcription activation</topic><topic>Transcription, Genetic - drug effects</topic><topic>Transfection</topic><topic>Tumors</topic><topic>Xenografts</topic><topic>Xenotransplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Jeong-Kook</creatorcontrib><creatorcontrib>Kim, Joon-Young</creatorcontrib><creatorcontrib>Kim, Han-Jong</creatorcontrib><creatorcontrib>Park, Keun-Gyu</creatorcontrib><creatorcontrib>Harris, Robert A</creatorcontrib><creatorcontrib>Cho, Won-Jea</creatorcontrib><creatorcontrib>Lee, Jae-Tae</creatorcontrib><creatorcontrib>Lee, In-Kyu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints Resource Center</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</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>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agriculture Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content 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><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Jeong-Kook</au><au>Kim, Joon-Young</au><au>Kim, Han-Jong</au><au>Park, Keun-Gyu</au><au>Harris, Robert A</au><au>Cho, Won-Jea</au><au>Lee, Jae-Tae</au><au>Lee, In-Kyu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Scoparone exerts anti-tumor activity against DU145 prostate cancer cells via inhibition of STAT3 activity</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-11-15</date><risdate>2013</risdate><volume>8</volume><issue>11</issue><spage>e80391</spage><pages>e80391-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><notes>Conceived and designed the experiments: JKK JYK HJK IKL. Performed the experiments: JKK WJC JTL. Analyzed the data: JKK WJC JTL JYK HJK IKL. Contributed reagents/materials/analysis tools: HJK RAH KGP. Wrote the manuscript: JKK JYK RAH IKL.</notes><notes>Competing Interests: The authors have declared that no competing interests exist.</notes><abstract>Scoparone, a natural compound isolated from Artemisia capillaris, has been used in Chinese herbal medicine to treat neonatal jaundice. Signal transducer and activator of transcription 3 (STAT3) contributes to the growth and survival of many human tumors. This study was undertaken to investigate the anti-tumor activity of scoparone against DU145 prostate cancer cells and to determine whether its effects are mediated by inhibition of STAT3 activity. Scoparone inhibited proliferation of DU145 cells via cell cycle arrest in G1 phase. Transient transfection assays showed that scoparone repressed both constitutive and IL-6-induced transcriptional activity of STAT3. Western blot and quantitative real-time PCR analyses demonstrated that scoparone suppressed the transcription of STAT3 target genes such as cyclin D1, c-Myc, survivin, Bcl-2, and Socs3. Consistent with this, scoparone decreased phosphorylation and nuclear accumulation of STAT3, but did not reduce phosphorylation of janus kinase 2 (JAK2) or Src, the major upstream kinases responsible for STAT3 activation. Moreover, transcriptional activity of a constitutively active mutant of STAT3 (STAT3C) was inhibited by scoparone, but not by AG490, a JAK2 inhibitor. Furthermore, scoparone treatment suppressed anchorage-independent growth in soft agar and tumor growth of DU145 xenografts in nude mice, concomitant with a reduction in STAT3 phosphorylation. Computational modeling suggested that scoparone might bind the SH2 domain of STAT3. Our findings suggest that scoparone elicits an anti-tumor effect against DU145 prostate cancer cells in part through inhibition of STAT3 activity.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24260381</pmid><doi>10.1371/journal.pone.0080391</doi><tpages>e80391</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-11, Vol.8 (11), p.e80391 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1458745582 |
| source | Publicly Available Content Database; PubMed Central |
| subjects | Agar Aging Androgens Animals Antibiotics Anticancer properties Antineoplastic Agents - pharmacology Antitumor agents Apoptosis Artemisia - chemistry Bcl-2 protein Breast cancer c-Myc protein Cancer Cancer cells Cancer prevention Cancer research Cancer therapies Cell cycle Cell Cycle Checkpoints - drug effects Cell Line, Tumor Cell proliferation Cell Proliferation - drug effects Computer applications Coumarins - pharmacology Cyclin D1 Cyclin D1 - metabolism Cytokines Epidermal growth factor G1 phase G1 Phase - drug effects HCT116 Cells HeLa Cells Hep G2 Cells Herbal medicine HT29 Cells Humans Inhibition Inhibitor of Apoptosis Proteins - metabolism Interleukin 6 Interleukin-6 - metabolism Internal medicine Janus kinase Janus kinase 2 Janus Kinase 2 - metabolism Jaundice Kinases Male MCF-7 Cells Medicine Metabolism Metastasis Mice Mice, Inbred BALB C Mice, Nude Mouse devices Myc protein Natural products Neonates Phosphorylation Phosphorylation - drug effects Prostate cancer Prostatic Neoplasms - drug therapy Prostatic Neoplasms - metabolism Proteins Proto-Oncogene Proteins c-bcl-2 - metabolism Proto-Oncogene Proteins c-myc - metabolism Rodents Signal Transduction - drug effects Stat3 protein STAT3 Transcription Factor - antagonists & inhibitors Suppressor of Cytokine Signaling 3 Protein Suppressor of Cytokine Signaling Proteins - metabolism Survivin Transcription (Genetics) Transcription activation Transcription, Genetic - drug effects Transfection Tumors Xenografts Xenotransplantation |
| title | Scoparone exerts anti-tumor activity against DU145 prostate cancer cells via inhibition of STAT3 activity |
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