Beta-elemene blocks epithelial-mesenchymal transition in human breast cancer cell line MCF-7 through Smad3-mediated down-regulation of nuclear transcription factors
Epithelial-mesenchymal transition (EMT) is the first step required for breast cancer to initiate metastasis. However, the potential of drugs to block and reverse the EMT process are not well explored. In the present study, we investigated the inhibitory effect of beta-elemene (ELE), an active compon...
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| creator | Zhang, Xian Li, Yinghua Zhang, Yang Song, Jincheng Wang, Qimin Zheng, Luping Liu, Dan |
| description | Epithelial-mesenchymal transition (EMT) is the first step required for breast cancer to initiate metastasis. However, the potential of drugs to block and reverse the EMT process are not well explored. In the present study, we investigated the inhibitory effect of beta-elemene (ELE), an active component of a natural plant-derived anti-neoplastic agent in an established EMT model mediated by transforming growth factor-beta1 (TGF-β1). We found that ELE (40 µg/ml ) blocked the TGF-β1-induced phenotypic transition in the human breast cancer cell line MCF-7. ELE was able to inhibit TGF-β1-mediated upregulation of mRNA and protein expression of nuclear transcription factors (SNAI1, SNAI2, TWIST and SIP1), potentially through decreasing the expression and phosphorylation of Smad3, a central protein mediating the TGF-β1 signalling pathway. These findings suggest a potential therapeutic benefit of ELE in treating basal-like breast cancer. |
| doi_str_mv | 10.1371/journal.pone.0058719 |
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However, the potential of drugs to block and reverse the EMT process are not well explored. In the present study, we investigated the inhibitory effect of beta-elemene (ELE), an active component of a natural plant-derived anti-neoplastic agent in an established EMT model mediated by transforming growth factor-beta1 (TGF-β1). We found that ELE (40 µg/ml ) blocked the TGF-β1-induced phenotypic transition in the human breast cancer cell line MCF-7. ELE was able to inhibit TGF-β1-mediated upregulation of mRNA and protein expression of nuclear transcription factors (SNAI1, SNAI2, TWIST and SIP1), potentially through decreasing the expression and phosphorylation of Smad3, a central protein mediating the TGF-β1 signalling pathway. These findings suggest a potential therapeutic benefit of ELE in treating basal-like breast cancer.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0058719</identifier><identifier>PMID: 23516540</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Antineoplastic Agents - pharmacology ; Apoptosis ; Biology ; Biotechnology ; Bone morphogenetic proteins ; Brain cancer ; Breast cancer ; Breast Neoplasms - pathology ; Cancer ; Cancer metastasis ; Cell cycle ; Cell Movement - drug effects ; Cooperation ; DNA binding proteins ; Down-Regulation - drug effects ; Drugs ; Epithelial-Mesenchymal Transition - drug effects ; Gene expression ; Gene regulation ; Growth factors ; Humans ; Immunoglobulins ; Lung cancer ; Mathematics ; MCF-7 Cells ; Medical prognosis ; Medicine ; Mesenchyme ; Metastases ; Metastasis ; Neoplasm Invasiveness ; Oncology ; Phenotype ; Phosphorylation ; Phosphorylation - drug effects ; Plants ; Sesquiterpenes - pharmacology ; Signal transduction ; Signaling ; Smad3 protein ; Snail protein ; snRNP Core Proteins - genetics ; snRNP Core Proteins - metabolism ; Stem cells ; Transcription factors ; Transcription Factors - genetics ; Transforming Growth Factor beta1 - pharmacology ; Transforming growth factor-b1 ; Transforming growth factors ; Up-Regulation - drug effects</subject><ispartof>PloS one, 2013-03, Vol.8 (3), p.e58719</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (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 Zhang et al 2013 Zhang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-1e1dd2ccd457d12caf58d9f8a93d38f2c500463ce8e931afc9fd2bb09e99f34b3</citedby><cites>FETCH-LOGICAL-c692t-1e1dd2ccd457d12caf58d9f8a93d38f2c500463ce8e931afc9fd2bb09e99f34b3</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/PMC3597725/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597725/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23516540$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Xian</creatorcontrib><creatorcontrib>Li, Yinghua</creatorcontrib><creatorcontrib>Zhang, Yang</creatorcontrib><creatorcontrib>Song, Jincheng</creatorcontrib><creatorcontrib>Wang, Qimin</creatorcontrib><creatorcontrib>Zheng, Luping</creatorcontrib><creatorcontrib>Liu, Dan</creatorcontrib><title>Beta-elemene blocks epithelial-mesenchymal transition in human breast cancer cell line MCF-7 through Smad3-mediated down-regulation of nuclear transcription factors</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Epithelial-mesenchymal transition (EMT) is the first step required for breast cancer to initiate metastasis. However, the potential of drugs to block and reverse the EMT process are not well explored. In the present study, we investigated the inhibitory effect of beta-elemene (ELE), an active component of a natural plant-derived anti-neoplastic agent in an established EMT model mediated by transforming growth factor-beta1 (TGF-β1). We found that ELE (40 µg/ml ) blocked the TGF-β1-induced phenotypic transition in the human breast cancer cell line MCF-7. ELE was able to inhibit TGF-β1-mediated upregulation of mRNA and protein expression of nuclear transcription factors (SNAI1, SNAI2, TWIST and SIP1), potentially through decreasing the expression and phosphorylation of Smad3, a central protein mediating the TGF-β1 signalling pathway. These findings suggest a potential therapeutic benefit of ELE in treating basal-like breast cancer.</description><subject>Analysis</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Biology</subject><subject>Biotechnology</subject><subject>Bone morphogenetic proteins</subject><subject>Brain cancer</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer</subject><subject>Cancer metastasis</subject><subject>Cell cycle</subject><subject>Cell Movement - drug effects</subject><subject>Cooperation</subject><subject>DNA binding proteins</subject><subject>Down-Regulation - drug effects</subject><subject>Drugs</subject><subject>Epithelial-Mesenchymal Transition - drug effects</subject><subject>Gene expression</subject><subject>Gene regulation</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Immunoglobulins</subject><subject>Lung cancer</subject><subject>Mathematics</subject><subject>MCF-7 Cells</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Mesenchyme</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Neoplasm Invasiveness</subject><subject>Oncology</subject><subject>Phenotype</subject><subject>Phosphorylation</subject><subject>Phosphorylation - drug effects</subject><subject>Plants</subject><subject>Sesquiterpenes - pharmacology</subject><subject>Signal transduction</subject><subject>Signaling</subject><subject>Smad3 protein</subject><subject>Snail protein</subject><subject>snRNP Core Proteins - genetics</subject><subject>snRNP Core Proteins - metabolism</subject><subject>Stem cells</subject><subject>Transcription factors</subject><subject>Transcription Factors - genetics</subject><subject>Transforming Growth Factor beta1 - pharmacology</subject><subject>Transforming growth factor-b1</subject><subject>Transforming growth factors</subject><subject>Up-Regulation - drug effects</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk92K1DAUgIso7rr6BqIBQfCiY9P0LzfCOrg6sLLgqrchTU6mGdNkTFJ138cHNfOzywwoSC4aku98OTnNybKnuJhh0uLXKzd5y81s7SzMiqLuWkzvZaeYkjJvyoLcP5ifZI9CWCWIdE3zMDspSY2buipOs99vIfIcDIxgAfXGiW8BwVrHAYzmJh8hgBXDzcgNip7boKN2FmmLhmnkFvUeeIhIcCvAIwHGIKOT6eP8Im9RHLyblgO6HrkkySU1jyCRdD9t7mE5Gb61OYXsJAxwvztDeL3ebiguovPhcfZAcRPgyf57ln25ePd5_iG_vHq_mJ9f5qKhZcwxYClLIWRVtxKXgqu6k1R1nBJJOlWKuiiqhgjogBLMlaBKln1fUKBUkaonZ9nznXdtXGD7AgeGCSk62pG2SsRiR0jHV2zt9cj9DXNcs-2C80vGfdTpLiz9ka5s-rZpSFUpXHR9W3UlrSvKaa0KnFxv9qdNfSqNAJsub46kxztWD2zpfjBS07Yt6yR4sRd4932CEP-R8p5a8pSVtsolmRh1EOy8arsyqZpNMrO_UGlIGLVIT0zptH4U8OooIDERfsUln0Jgi-tP_89efT1mXx6wA3ATh-DMtHkP4RisdqDwLgQP6q5yuGCbDrmtBtt0CNt3SAp7dlj1u6DbliB_AOMcDqs</recordid><startdate>20130314</startdate><enddate>20130314</enddate><creator>Zhang, Xian</creator><creator>Li, Yinghua</creator><creator>Zhang, Yang</creator><creator>Song, Jincheng</creator><creator>Wang, Qimin</creator><creator>Zheng, Luping</creator><creator>Liu, Dan</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>AEUYN</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>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</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>20130314</creationdate><title>Beta-elemene blocks epithelial-mesenchymal transition in human breast cancer cell line MCF-7 through Smad3-mediated down-regulation of nuclear transcription factors</title><author>Zhang, Xian ; Li, Yinghua ; Zhang, Yang ; Song, Jincheng ; Wang, Qimin ; Zheng, Luping ; Liu, Dan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-1e1dd2ccd457d12caf58d9f8a93d38f2c500463ce8e931afc9fd2bb09e99f34b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Analysis</topic><topic>Antineoplastic Agents - 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However, the potential of drugs to block and reverse the EMT process are not well explored. In the present study, we investigated the inhibitory effect of beta-elemene (ELE), an active component of a natural plant-derived anti-neoplastic agent in an established EMT model mediated by transforming growth factor-beta1 (TGF-β1). We found that ELE (40 µg/ml ) blocked the TGF-β1-induced phenotypic transition in the human breast cancer cell line MCF-7. ELE was able to inhibit TGF-β1-mediated upregulation of mRNA and protein expression of nuclear transcription factors (SNAI1, SNAI2, TWIST and SIP1), potentially through decreasing the expression and phosphorylation of Smad3, a central protein mediating the TGF-β1 signalling pathway. These findings suggest a potential therapeutic benefit of ELE in treating basal-like breast cancer.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23516540</pmid><doi>10.1371/journal.pone.0058719</doi><tpages>e58719</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Analysis Antineoplastic Agents - pharmacology Apoptosis Biology Biotechnology Bone morphogenetic proteins Brain cancer Breast cancer Breast Neoplasms - pathology Cancer Cancer metastasis Cell cycle Cell Movement - drug effects Cooperation DNA binding proteins Down-Regulation - drug effects Drugs Epithelial-Mesenchymal Transition - drug effects Gene expression Gene regulation Growth factors Humans Immunoglobulins Lung cancer Mathematics MCF-7 Cells Medical prognosis Medicine Mesenchyme Metastases Metastasis Neoplasm Invasiveness Oncology Phenotype Phosphorylation Phosphorylation - drug effects Plants Sesquiterpenes - pharmacology Signal transduction Signaling Smad3 protein Snail protein snRNP Core Proteins - genetics snRNP Core Proteins - metabolism Stem cells Transcription factors Transcription Factors - genetics Transforming Growth Factor beta1 - pharmacology Transforming growth factor-b1 Transforming growth factors Up-Regulation - drug effects |
| title | Beta-elemene blocks epithelial-mesenchymal transition in human breast cancer cell line MCF-7 through Smad3-mediated down-regulation of nuclear transcription factors |
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