(-)-Oleocanthal inhibits growth and metastasis by blocking activation of STAT3 in human hepatocellular carcinoma
We explored the anti-cancer capacity of (-)-oleocanthal in human hepatocellular carcinoma (HCC). (-)-Oleocanthal inhibited proliferation and cell cycle progression and induced apoptosis in HCC cells in vitro and suppressed tumor growth in an orthotopic HCC model. (-)-Oleocanthal also inhibited HCC c...
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| Veröffentlicht in: | Oncotarget 2016-07, Vol.7 (28), p.43475-43491 |
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| creator | Pei, Tiemin Meng, Qinghui Han, Jihua Sun, Haobo Li, Long Song, Ruipeng Sun, Boshi Pan, Shangha Liang, Desen Liu, Lianxin |
| description | We explored the anti-cancer capacity of (-)-oleocanthal in human hepatocellular carcinoma (HCC). (-)-Oleocanthal inhibited proliferation and cell cycle progression and induced apoptosis in HCC cells in vitro and suppressed tumor growth in an orthotopic HCC model. (-)-Oleocanthal also inhibited HCC cell migration and invasion in vitro and impeded HCC metastasis in an in vivo lung metastasis model. ( )-Oleocanthal acted by inhibiting epithelial-mesenchymal transition (EMT) through downregulation Twist, which is a direct target of STAT3. (-)-Oleocanthal also reduced STAT3 nuclear translocation and DNA binding activity, ultimately downregulating its downstream effectors, including the cell cycle protein Cyclin D1, the anti-apoptotic proteins Bcl-2 and survivin, and the invasion-related protein MMP 2. Overexpression of constitutively active STAT3 partly reversed the anti cancer effects of (-)-oleocanthal, which inhibited STAT3 activation by decreasing the activities of JAK1 and JAK2 and increasing the activity of SHP-1. These data suggest that (-)-oleocanthal may be a promising candidate for HCC treatment. |
| doi_str_mv | 10.18632/oncotarget.9782 |
| format | Article |
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(-)-Oleocanthal inhibited proliferation and cell cycle progression and induced apoptosis in HCC cells in vitro and suppressed tumor growth in an orthotopic HCC model. (-)-Oleocanthal also inhibited HCC cell migration and invasion in vitro and impeded HCC metastasis in an in vivo lung metastasis model. ( )-Oleocanthal acted by inhibiting epithelial-mesenchymal transition (EMT) through downregulation Twist, which is a direct target of STAT3. (-)-Oleocanthal also reduced STAT3 nuclear translocation and DNA binding activity, ultimately downregulating its downstream effectors, including the cell cycle protein Cyclin D1, the anti-apoptotic proteins Bcl-2 and survivin, and the invasion-related protein MMP 2. Overexpression of constitutively active STAT3 partly reversed the anti cancer effects of (-)-oleocanthal, which inhibited STAT3 activation by decreasing the activities of JAK1 and JAK2 and increasing the activity of SHP-1. These data suggest that (-)-oleocanthal may be a promising candidate for HCC treatment.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.9782</identifier><identifier>PMID: 27259268</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Aldehydes - isolation & purification ; Aldehydes - therapeutic use ; Animals ; Antineoplastic Agents - therapeutic use ; Apoptosis - drug effects ; Carcinoma, Hepatocellular - drug therapy ; Carcinoma, Hepatocellular - pathology ; Cell Cycle - drug effects ; Cell Line, Tumor ; Cell Movement - drug effects ; Cell Nucleus - metabolism ; Cell Proliferation - drug effects ; Cyclin D1 - metabolism ; Down-Regulation ; Epithelial-Mesenchymal Transition - drug effects ; Humans ; Inhibitor of Apoptosis Proteins - metabolism ; Janus Kinase 1 - metabolism ; Janus Kinase 2 - metabolism ; Liver Neoplasms - drug therapy ; Liver Neoplasms - pathology ; Lung Neoplasms - prevention & control ; Lung Neoplasms - secondary ; Male ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Invasiveness - prevention & control ; Nuclear Proteins - metabolism ; Olive Oil - chemistry ; Phenols - isolation & purification ; Phenols - therapeutic use ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 - metabolism ; Proto-Oncogene Proteins c-akt ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Research Paper ; STAT3 Transcription Factor - genetics ; STAT3 Transcription Factor - metabolism ; Survivin ; Twist-Related Protein 1 - metabolism ; Xenograft Model Antitumor Assays</subject><ispartof>Oncotarget, 2016-07, Vol.7 (28), p.43475-43491</ispartof><rights>Copyright: © 2016 Pei et al. 2016</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c354t-1093d8ee99a7aabf8d34003377ea0030ecd6cbe512a1ebd06b865ee21019091b3</citedby><cites>FETCH-LOGICAL-c354t-1093d8ee99a7aabf8d34003377ea0030ecd6cbe512a1ebd06b865ee21019091b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5190038/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5190038/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27259268$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pei, Tiemin</creatorcontrib><creatorcontrib>Meng, Qinghui</creatorcontrib><creatorcontrib>Han, Jihua</creatorcontrib><creatorcontrib>Sun, Haobo</creatorcontrib><creatorcontrib>Li, Long</creatorcontrib><creatorcontrib>Song, Ruipeng</creatorcontrib><creatorcontrib>Sun, Boshi</creatorcontrib><creatorcontrib>Pan, Shangha</creatorcontrib><creatorcontrib>Liang, Desen</creatorcontrib><creatorcontrib>Liu, Lianxin</creatorcontrib><title>(-)-Oleocanthal inhibits growth and metastasis by blocking activation of STAT3 in human hepatocellular carcinoma</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>We explored the anti-cancer capacity of (-)-oleocanthal in human hepatocellular carcinoma (HCC). (-)-Oleocanthal inhibited proliferation and cell cycle progression and induced apoptosis in HCC cells in vitro and suppressed tumor growth in an orthotopic HCC model. (-)-Oleocanthal also inhibited HCC cell migration and invasion in vitro and impeded HCC metastasis in an in vivo lung metastasis model. ( )-Oleocanthal acted by inhibiting epithelial-mesenchymal transition (EMT) through downregulation Twist, which is a direct target of STAT3. (-)-Oleocanthal also reduced STAT3 nuclear translocation and DNA binding activity, ultimately downregulating its downstream effectors, including the cell cycle protein Cyclin D1, the anti-apoptotic proteins Bcl-2 and survivin, and the invasion-related protein MMP 2. Overexpression of constitutively active STAT3 partly reversed the anti cancer effects of (-)-oleocanthal, which inhibited STAT3 activation by decreasing the activities of JAK1 and JAK2 and increasing the activity of SHP-1. These data suggest that (-)-oleocanthal may be a promising candidate for HCC treatment.</description><subject>Aldehydes - isolation & purification</subject><subject>Aldehydes - therapeutic use</subject><subject>Animals</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Apoptosis - drug effects</subject><subject>Carcinoma, Hepatocellular - drug therapy</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Cell Nucleus - metabolism</subject><subject>Cell Proliferation - drug effects</subject><subject>Cyclin D1 - metabolism</subject><subject>Down-Regulation</subject><subject>Epithelial-Mesenchymal Transition - drug effects</subject><subject>Humans</subject><subject>Inhibitor of Apoptosis Proteins - metabolism</subject><subject>Janus Kinase 1 - metabolism</subject><subject>Janus Kinase 2 - metabolism</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - pathology</subject><subject>Lung Neoplasms - prevention & control</subject><subject>Lung Neoplasms - secondary</subject><subject>Male</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Neoplasm Invasiveness - prevention & control</subject><subject>Nuclear Proteins - metabolism</subject><subject>Olive Oil - chemistry</subject><subject>Phenols - isolation & purification</subject><subject>Phenols - therapeutic use</subject><subject>Protein Tyrosine Phosphatase, Non-Receptor Type 6 - metabolism</subject><subject>Proto-Oncogene Proteins c-akt</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Research Paper</subject><subject>STAT3 Transcription Factor - genetics</subject><subject>STAT3 Transcription Factor - metabolism</subject><subject>Survivin</subject><subject>Twist-Related Protein 1 - metabolism</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUU1P3DAQtaoiQMC9p8pHegj1xyaxL0gIlbYSEoduz9bYmd24TezFdqj495jyUWqNPCPNe29m9Aj5wNkZV50Un2NwsUDaYjnTvRLvyCHXK92ItpXv39QH5CTnX6y-dlVhep8ciF60WnTqkOxOm0_NzYTRQSgjTNSH0VtfMt2m-KeMFMJAZyyQa_hM7T21U3S_fdhScMXfQfEx0LihP9YXa1npdFxmqD_uoESH07RMkKiD5HyIMxyTvQ1MGU-e8xH5efVlffmtub75-v3y4rpxsl2VhjMtB4WoNfQAdqMGuWJMyr5HqJmhGzpnseUCONqBdVZ1LaLgjGumuZVH5PxJd7fYGQeHoSSYzC75GdK9ieDN_53gR7ONd6atAkyqKnD6LJDi7YK5mNnnx3sgYFyy4Up0ndJadhXKnqAuxZwTbl7HcGb-emX-eWUevaqUj2_XeyW8OCMfALFZlQo</recordid><startdate>20160712</startdate><enddate>20160712</enddate><creator>Pei, Tiemin</creator><creator>Meng, Qinghui</creator><creator>Han, Jihua</creator><creator>Sun, Haobo</creator><creator>Li, Long</creator><creator>Song, Ruipeng</creator><creator>Sun, Boshi</creator><creator>Pan, Shangha</creator><creator>Liang, Desen</creator><creator>Liu, Lianxin</creator><general>Impact Journals LLC</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160712</creationdate><title>(-)-Oleocanthal inhibits growth and metastasis by blocking activation of STAT3 in human hepatocellular carcinoma</title><author>Pei, Tiemin ; Meng, Qinghui ; Han, Jihua ; Sun, Haobo ; Li, Long ; Song, Ruipeng ; Sun, Boshi ; Pan, Shangha ; Liang, Desen ; Liu, Lianxin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c354t-1093d8ee99a7aabf8d34003377ea0030ecd6cbe512a1ebd06b865ee21019091b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Aldehydes - isolation & purification</topic><topic>Aldehydes - therapeutic use</topic><topic>Animals</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Apoptosis - drug effects</topic><topic>Carcinoma, Hepatocellular - drug therapy</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Cell Cycle - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - drug effects</topic><topic>Cell Nucleus - metabolism</topic><topic>Cell Proliferation - drug effects</topic><topic>Cyclin D1 - metabolism</topic><topic>Down-Regulation</topic><topic>Epithelial-Mesenchymal Transition - drug effects</topic><topic>Humans</topic><topic>Inhibitor of Apoptosis Proteins - metabolism</topic><topic>Janus Kinase 1 - metabolism</topic><topic>Janus Kinase 2 - metabolism</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - pathology</topic><topic>Lung Neoplasms - prevention & control</topic><topic>Lung Neoplasms - secondary</topic><topic>Male</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Neoplasm Invasiveness - prevention & control</topic><topic>Nuclear Proteins - metabolism</topic><topic>Olive Oil - chemistry</topic><topic>Phenols - isolation & purification</topic><topic>Phenols - therapeutic use</topic><topic>Protein Tyrosine Phosphatase, Non-Receptor Type 6 - metabolism</topic><topic>Proto-Oncogene Proteins c-akt</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><topic>Research Paper</topic><topic>STAT3 Transcription Factor - genetics</topic><topic>STAT3 Transcription Factor - metabolism</topic><topic>Survivin</topic><topic>Twist-Related Protein 1 - metabolism</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>online_resources</toplevel><creatorcontrib>Pei, Tiemin</creatorcontrib><creatorcontrib>Meng, Qinghui</creatorcontrib><creatorcontrib>Han, Jihua</creatorcontrib><creatorcontrib>Sun, Haobo</creatorcontrib><creatorcontrib>Li, Long</creatorcontrib><creatorcontrib>Song, Ruipeng</creatorcontrib><creatorcontrib>Sun, Boshi</creatorcontrib><creatorcontrib>Pan, Shangha</creatorcontrib><creatorcontrib>Liang, Desen</creatorcontrib><creatorcontrib>Liu, Lianxin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pei, Tiemin</au><au>Meng, Qinghui</au><au>Han, Jihua</au><au>Sun, Haobo</au><au>Li, Long</au><au>Song, Ruipeng</au><au>Sun, Boshi</au><au>Pan, Shangha</au><au>Liang, Desen</au><au>Liu, Lianxin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>(-)-Oleocanthal inhibits growth and metastasis by blocking activation of STAT3 in human hepatocellular carcinoma</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2016-07-12</date><risdate>2016</risdate><volume>7</volume><issue>28</issue><spage>43475</spage><epage>43491</epage><pages>43475-43491</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>We explored the anti-cancer capacity of (-)-oleocanthal in human hepatocellular carcinoma (HCC). (-)-Oleocanthal inhibited proliferation and cell cycle progression and induced apoptosis in HCC cells in vitro and suppressed tumor growth in an orthotopic HCC model. (-)-Oleocanthal also inhibited HCC cell migration and invasion in vitro and impeded HCC metastasis in an in vivo lung metastasis model. ( )-Oleocanthal acted by inhibiting epithelial-mesenchymal transition (EMT) through downregulation Twist, which is a direct target of STAT3. (-)-Oleocanthal also reduced STAT3 nuclear translocation and DNA binding activity, ultimately downregulating its downstream effectors, including the cell cycle protein Cyclin D1, the anti-apoptotic proteins Bcl-2 and survivin, and the invasion-related protein MMP 2. Overexpression of constitutively active STAT3 partly reversed the anti cancer effects of (-)-oleocanthal, which inhibited STAT3 activation by decreasing the activities of JAK1 and JAK2 and increasing the activity of SHP-1. These data suggest that (-)-oleocanthal may be a promising candidate for HCC treatment.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>27259268</pmid><doi>10.18632/oncotarget.9782</doi><tpages>17</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aldehydes - isolation & purification Aldehydes - therapeutic use Animals Antineoplastic Agents - therapeutic use Apoptosis - drug effects Carcinoma, Hepatocellular - drug therapy Carcinoma, Hepatocellular - pathology Cell Cycle - drug effects Cell Line, Tumor Cell Movement - drug effects Cell Nucleus - metabolism Cell Proliferation - drug effects Cyclin D1 - metabolism Down-Regulation Epithelial-Mesenchymal Transition - drug effects Humans Inhibitor of Apoptosis Proteins - metabolism Janus Kinase 1 - metabolism Janus Kinase 2 - metabolism Liver Neoplasms - drug therapy Liver Neoplasms - pathology Lung Neoplasms - prevention & control Lung Neoplasms - secondary Male Mice, Inbred BALB C Mice, Nude Neoplasm Invasiveness - prevention & control Nuclear Proteins - metabolism Olive Oil - chemistry Phenols - isolation & purification Phenols - therapeutic use Protein Tyrosine Phosphatase, Non-Receptor Type 6 - metabolism Proto-Oncogene Proteins c-akt Proto-Oncogene Proteins c-bcl-2 - metabolism Research Paper STAT3 Transcription Factor - genetics STAT3 Transcription Factor - metabolism Survivin Twist-Related Protein 1 - metabolism Xenograft Model Antitumor Assays |
| title | (-)-Oleocanthal inhibits growth and metastasis by blocking activation of STAT3 in human hepatocellular carcinoma |
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