Geraniin inhibits oral cancer cell migration by suppressing matrix metalloproteinase‐2 activation through the FAK/Src and ERK pathways
Geraniin has been reported to have numerous biological activities, including antiviral, antihypertensive, antihyperglycaemic, liver protective, antidiabetic, and apoptotic activities. However, the anti‐migration effects of geraniin on oral cancer remain elusive. In this study, we revealed the potent...
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| Veröffentlicht in: | Environmental toxicology 2019-10, Vol.34 (10), p.1085-1093 |
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| creator | Yeh, Chia‐Ming Hsieh, Ming‐Ju Yang, Jia‐Sin Yang, Shun‐Fa Chuang, Yi‐Ting Su, Shih‐Chi Liang, Meng‐Yuan Chen, Mu‐Kuan Lin, Chiao‐Wen |
| description | Geraniin has been reported to have numerous biological activities, including antiviral, antihypertensive, antihyperglycaemic, liver protective, antidiabetic, and apoptotic activities. However, the anti‐migration effects of geraniin on oral cancer remain elusive. In this study, we revealed the potential antitumor mechanisms of geraniin through the inhibition of the migration and invasion of human oral cancer cell lines SCC‐9 and SCC‐14. The results of gelatin zymography and Western blot assays revealed that geraniin significantly reduced the activity and expression of matrix metalloproteinase‐2 (MMP‐2) of oral cancer cells in a concentration‐dependent manner. Furthermore, geraniin potently suppressed the phosphorylation of focal adhesion kinase (FAK), Src, and extracellular signal‐regulated kinase (ERK)1/2 but did not affect the phosphorylation of p38 mitogen‐activated protein kinase (MAPK) and c‐Jun N‐terminal kinase 1/2. Moreover, blocking the MAPK/ERK1/2 pathway significantly enhanced the anti‐migration ability of geraniin in oral cancer cells. In conclusion, we demonstrated that geraniin inhibits the motility of SCC‐9 and SCC‐14 cells in vitro through a molecular mechanism that involves the attenuation of MMP‐2 expression and activity mediated by decreased FAK/Src and ERK1/2 pathways. |
| doi_str_mv | 10.1002/tox.22809 |
| format | Article |
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However, the anti‐migration effects of geraniin on oral cancer remain elusive. In this study, we revealed the potential antitumor mechanisms of geraniin through the inhibition of the migration and invasion of human oral cancer cell lines SCC‐9 and SCC‐14. The results of gelatin zymography and Western blot assays revealed that geraniin significantly reduced the activity and expression of matrix metalloproteinase‐2 (MMP‐2) of oral cancer cells in a concentration‐dependent manner. Furthermore, geraniin potently suppressed the phosphorylation of focal adhesion kinase (FAK), Src, and extracellular signal‐regulated kinase (ERK)1/2 but did not affect the phosphorylation of p38 mitogen‐activated protein kinase (MAPK) and c‐Jun N‐terminal kinase 1/2. Moreover, blocking the MAPK/ERK1/2 pathway significantly enhanced the anti‐migration ability of geraniin in oral cancer cells. In conclusion, we demonstrated that geraniin inhibits the motility of SCC‐9 and SCC‐14 cells in vitro through a molecular mechanism that involves the attenuation of MMP‐2 expression and activity mediated by decreased FAK/Src and ERK1/2 pathways.</description><identifier>ISSN: 1520-4081</identifier><identifier>EISSN: 1522-7278</identifier><identifier>DOI: 10.1002/tox.22809</identifier><identifier>PMID: 31184425</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Antidiabetics ; Antihypertensives ; Antineoplastic Agents - pharmacology ; Antitumor activity ; Antitumour agents ; Antiviral agents ; Apoptosis ; Attenuation ; Cancer ; Cell adhesion & migration ; Cell Line, Tumor ; Cell lines ; Cell migration ; Cell Movement - drug effects ; Cells ; Diabetes mellitus ; Drugs, Chinese Herbal - pharmacology ; ERK1/2 pathway ; Extracellular ; Extracellular signal-regulated kinase ; Focal adhesion kinase ; Focal Adhesion Protein-Tyrosine Kinases - genetics ; Focal Adhesion Protein-Tyrosine Kinases - metabolism ; Gelatin ; geraniin ; Geranium - chemistry ; Glucosides - pharmacology ; Humans ; Hydrolyzable Tannins - pharmacology ; JNK protein ; Kinases ; MAP kinase ; MAP Kinase Signaling System - drug effects ; Matrix metalloproteinase ; Matrix Metalloproteinase 2 - genetics ; Matrix Metalloproteinase 2 - metabolism ; Matrix metalloproteinases ; Metabolic pathways ; Metalloproteinase ; migration ; Mitogen-Activated Protein Kinase 3 - metabolism ; Mitogen-Activated Protein Kinases - genetics ; Mitogen-Activated Protein Kinases - metabolism ; MMP‐2 ; Mouth Neoplasms - genetics ; Mouth Neoplasms - metabolism ; Mouth Neoplasms - physiopathology ; Oral cancer ; Phosphorylation ; Protein kinase ; Src protein ; src-Family Kinases - genetics ; src-Family Kinases - metabolism ; Tumor cell lines</subject><ispartof>Environmental toxicology, 2019-10, Vol.34 (10), p.1085-1093</ispartof><rights>2019 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4569-d68e7829a60435aac14c131c165d5a034b862f237371ed7d440927b790fd2c363</citedby><cites>FETCH-LOGICAL-c4569-d68e7829a60435aac14c131c165d5a034b862f237371ed7d440927b790fd2c363</cites><orcidid>0000-0001-9726-3234</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Ftox.22809$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Ftox.22809$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31184425$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yeh, Chia‐Ming</creatorcontrib><creatorcontrib>Hsieh, Ming‐Ju</creatorcontrib><creatorcontrib>Yang, Jia‐Sin</creatorcontrib><creatorcontrib>Yang, Shun‐Fa</creatorcontrib><creatorcontrib>Chuang, Yi‐Ting</creatorcontrib><creatorcontrib>Su, Shih‐Chi</creatorcontrib><creatorcontrib>Liang, Meng‐Yuan</creatorcontrib><creatorcontrib>Chen, Mu‐Kuan</creatorcontrib><creatorcontrib>Lin, Chiao‐Wen</creatorcontrib><title>Geraniin inhibits oral cancer cell migration by suppressing matrix metalloproteinase‐2 activation through the FAK/Src and ERK pathways</title><title>Environmental toxicology</title><addtitle>Environ Toxicol</addtitle><description>Geraniin has been reported to have numerous biological activities, including antiviral, antihypertensive, antihyperglycaemic, liver protective, antidiabetic, and apoptotic activities. However, the anti‐migration effects of geraniin on oral cancer remain elusive. In this study, we revealed the potential antitumor mechanisms of geraniin through the inhibition of the migration and invasion of human oral cancer cell lines SCC‐9 and SCC‐14. The results of gelatin zymography and Western blot assays revealed that geraniin significantly reduced the activity and expression of matrix metalloproteinase‐2 (MMP‐2) of oral cancer cells in a concentration‐dependent manner. Furthermore, geraniin potently suppressed the phosphorylation of focal adhesion kinase (FAK), Src, and extracellular signal‐regulated kinase (ERK)1/2 but did not affect the phosphorylation of p38 mitogen‐activated protein kinase (MAPK) and c‐Jun N‐terminal kinase 1/2. Moreover, blocking the MAPK/ERK1/2 pathway significantly enhanced the anti‐migration ability of geraniin in oral cancer cells. In conclusion, we demonstrated that geraniin inhibits the motility of SCC‐9 and SCC‐14 cells in vitro through a molecular mechanism that involves the attenuation of MMP‐2 expression and activity mediated by decreased FAK/Src and ERK1/2 pathways.</description><subject>Antidiabetics</subject><subject>Antihypertensives</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antitumor activity</subject><subject>Antitumour agents</subject><subject>Antiviral agents</subject><subject>Apoptosis</subject><subject>Attenuation</subject><subject>Cancer</subject><subject>Cell adhesion & migration</subject><subject>Cell Line, Tumor</subject><subject>Cell lines</subject><subject>Cell migration</subject><subject>Cell Movement - drug effects</subject><subject>Cells</subject><subject>Diabetes mellitus</subject><subject>Drugs, Chinese Herbal - pharmacology</subject><subject>ERK1/2 pathway</subject><subject>Extracellular</subject><subject>Extracellular signal-regulated kinase</subject><subject>Focal adhesion kinase</subject><subject>Focal Adhesion Protein-Tyrosine Kinases - genetics</subject><subject>Focal Adhesion Protein-Tyrosine Kinases - metabolism</subject><subject>Gelatin</subject><subject>geraniin</subject><subject>Geranium - chemistry</subject><subject>Glucosides - pharmacology</subject><subject>Humans</subject><subject>Hydrolyzable Tannins - pharmacology</subject><subject>JNK protein</subject><subject>Kinases</subject><subject>MAP kinase</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Matrix metalloproteinase</subject><subject>Matrix Metalloproteinase 2 - genetics</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Matrix metalloproteinases</subject><subject>Metabolic pathways</subject><subject>Metalloproteinase</subject><subject>migration</subject><subject>Mitogen-Activated Protein Kinase 3 - metabolism</subject><subject>Mitogen-Activated Protein Kinases - genetics</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>MMP‐2</subject><subject>Mouth Neoplasms - genetics</subject><subject>Mouth Neoplasms - metabolism</subject><subject>Mouth Neoplasms - physiopathology</subject><subject>Oral cancer</subject><subject>Phosphorylation</subject><subject>Protein kinase</subject><subject>Src protein</subject><subject>src-Family Kinases - genetics</subject><subject>src-Family Kinases - metabolism</subject><subject>Tumor cell lines</subject><issn>1520-4081</issn><issn>1522-7278</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kb1OHTEQha0oUSAkRV4gspQmKZY7_tm_EiEgCCQkQqR0q1mv771Gu_bG9gK3S0nJM-ZJ8GVJCqRUM8U3R2fOIeQjg30GwBfR3e1zXkH9iuyynPOs5GX1-mmHTELFdsi7EK4BoC7y4i3ZEYxVUvJ8l9yfaI_WGEuNXZvWxECdx54qtEp7qnTf08GsPEbjLG03NEzj6HUIxq7ogNGbOzroiH3vRu-iNhaD_vP7gVNU0dzMZ3Ht3bRap6np8cHZ4rtXFG1Hjy7P6IhxfYub8J68WWIf9IfnuUd-HB9dHX7Lzi9OTg8PzjMl86LOuqLSZcVrLECKHFExqZhgihV5lyMI2VYFX3JRipLpruykhJqXbVnDsuNKFGKPfJl1k91fkw6xGUzYvolWuyk0Kcc8xSSgTujnF-i1m7xN7rZUyq_mAIn6OlPKuxC8XjajNwP6TcOg2dbTpHqap3oS--lZcWoH3f0j__aRgMUM3Jpeb_6v1Fxd_JwlHwGfrJrr</recordid><startdate>201910</startdate><enddate>201910</enddate><creator>Yeh, Chia‐Ming</creator><creator>Hsieh, Ming‐Ju</creator><creator>Yang, Jia‐Sin</creator><creator>Yang, Shun‐Fa</creator><creator>Chuang, Yi‐Ting</creator><creator>Su, Shih‐Chi</creator><creator>Liang, Meng‐Yuan</creator><creator>Chen, Mu‐Kuan</creator><creator>Lin, Chiao‐Wen</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</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>7QH</scope><scope>7ST</scope><scope>7TN</scope><scope>7U7</scope><scope>7UA</scope><scope>C1K</scope><scope>F1W</scope><scope>H97</scope><scope>K9.</scope><scope>L.G</scope><scope>M7N</scope><scope>SOI</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9726-3234</orcidid></search><sort><creationdate>201910</creationdate><title>Geraniin inhibits oral cancer cell migration by suppressing matrix metalloproteinase‐2 activation through the FAK/Src and ERK pathways</title><author>Yeh, Chia‐Ming ; Hsieh, Ming‐Ju ; Yang, Jia‐Sin ; Yang, Shun‐Fa ; Chuang, Yi‐Ting ; Su, Shih‐Chi ; Liang, Meng‐Yuan ; Chen, Mu‐Kuan ; Lin, Chiao‐Wen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4569-d68e7829a60435aac14c131c165d5a034b862f237371ed7d440927b790fd2c363</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Antidiabetics</topic><topic>Antihypertensives</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antitumor activity</topic><topic>Antitumour agents</topic><topic>Antiviral agents</topic><topic>Apoptosis</topic><topic>Attenuation</topic><topic>Cancer</topic><topic>Cell adhesion & migration</topic><topic>Cell Line, Tumor</topic><topic>Cell lines</topic><topic>Cell migration</topic><topic>Cell Movement - drug effects</topic><topic>Cells</topic><topic>Diabetes mellitus</topic><topic>Drugs, Chinese Herbal - pharmacology</topic><topic>ERK1/2 pathway</topic><topic>Extracellular</topic><topic>Extracellular signal-regulated kinase</topic><topic>Focal adhesion kinase</topic><topic>Focal Adhesion Protein-Tyrosine Kinases - genetics</topic><topic>Focal Adhesion Protein-Tyrosine Kinases - metabolism</topic><topic>Gelatin</topic><topic>geraniin</topic><topic>Geranium - chemistry</topic><topic>Glucosides - pharmacology</topic><topic>Humans</topic><topic>Hydrolyzable Tannins - pharmacology</topic><topic>JNK protein</topic><topic>Kinases</topic><topic>MAP kinase</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Matrix metalloproteinase</topic><topic>Matrix Metalloproteinase 2 - genetics</topic><topic>Matrix Metalloproteinase 2 - metabolism</topic><topic>Matrix metalloproteinases</topic><topic>Metabolic pathways</topic><topic>Metalloproteinase</topic><topic>migration</topic><topic>Mitogen-Activated Protein Kinase 3 - metabolism</topic><topic>Mitogen-Activated Protein Kinases - genetics</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>MMP‐2</topic><topic>Mouth Neoplasms - genetics</topic><topic>Mouth Neoplasms - metabolism</topic><topic>Mouth Neoplasms - physiopathology</topic><topic>Oral cancer</topic><topic>Phosphorylation</topic><topic>Protein kinase</topic><topic>Src protein</topic><topic>src-Family Kinases - genetics</topic><topic>src-Family Kinases - metabolism</topic><topic>Tumor cell lines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yeh, Chia‐Ming</creatorcontrib><creatorcontrib>Hsieh, Ming‐Ju</creatorcontrib><creatorcontrib>Yang, Jia‐Sin</creatorcontrib><creatorcontrib>Yang, Shun‐Fa</creatorcontrib><creatorcontrib>Chuang, Yi‐Ting</creatorcontrib><creatorcontrib>Su, Shih‐Chi</creatorcontrib><creatorcontrib>Liang, Meng‐Yuan</creatorcontrib><creatorcontrib>Chen, Mu‐Kuan</creatorcontrib><creatorcontrib>Lin, Chiao‐Wen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aqualine</collection><collection>Environment Abstracts</collection><collection>Oceanic Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Water Resources Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Environmental toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yeh, Chia‐Ming</au><au>Hsieh, Ming‐Ju</au><au>Yang, Jia‐Sin</au><au>Yang, Shun‐Fa</au><au>Chuang, Yi‐Ting</au><au>Su, Shih‐Chi</au><au>Liang, Meng‐Yuan</au><au>Chen, Mu‐Kuan</au><au>Lin, Chiao‐Wen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Geraniin inhibits oral cancer cell migration by suppressing matrix metalloproteinase‐2 activation through the FAK/Src and ERK pathways</atitle><jtitle>Environmental toxicology</jtitle><addtitle>Environ Toxicol</addtitle><date>2019-10</date><risdate>2019</risdate><volume>34</volume><issue>10</issue><spage>1085</spage><epage>1093</epage><pages>1085-1093</pages><issn>1520-4081</issn><eissn>1522-7278</eissn><abstract>Geraniin has been reported to have numerous biological activities, including antiviral, antihypertensive, antihyperglycaemic, liver protective, antidiabetic, and apoptotic activities. However, the anti‐migration effects of geraniin on oral cancer remain elusive. In this study, we revealed the potential antitumor mechanisms of geraniin through the inhibition of the migration and invasion of human oral cancer cell lines SCC‐9 and SCC‐14. The results of gelatin zymography and Western blot assays revealed that geraniin significantly reduced the activity and expression of matrix metalloproteinase‐2 (MMP‐2) of oral cancer cells in a concentration‐dependent manner. Furthermore, geraniin potently suppressed the phosphorylation of focal adhesion kinase (FAK), Src, and extracellular signal‐regulated kinase (ERK)1/2 but did not affect the phosphorylation of p38 mitogen‐activated protein kinase (MAPK) and c‐Jun N‐terminal kinase 1/2. Moreover, blocking the MAPK/ERK1/2 pathway significantly enhanced the anti‐migration ability of geraniin in oral cancer cells. In conclusion, we demonstrated that geraniin inhibits the motility of SCC‐9 and SCC‐14 cells in vitro through a molecular mechanism that involves the attenuation of MMP‐2 expression and activity mediated by decreased FAK/Src and ERK1/2 pathways.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>31184425</pmid><doi>10.1002/tox.22809</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-9726-3234</orcidid></addata></record> |
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| subjects | Antidiabetics Antihypertensives Antineoplastic Agents - pharmacology Antitumor activity Antitumour agents Antiviral agents Apoptosis Attenuation Cancer Cell adhesion & migration Cell Line, Tumor Cell lines Cell migration Cell Movement - drug effects Cells Diabetes mellitus Drugs, Chinese Herbal - pharmacology ERK1/2 pathway Extracellular Extracellular signal-regulated kinase Focal adhesion kinase Focal Adhesion Protein-Tyrosine Kinases - genetics Focal Adhesion Protein-Tyrosine Kinases - metabolism Gelatin geraniin Geranium - chemistry Glucosides - pharmacology Humans Hydrolyzable Tannins - pharmacology JNK protein Kinases MAP kinase MAP Kinase Signaling System - drug effects Matrix metalloproteinase Matrix Metalloproteinase 2 - genetics Matrix Metalloproteinase 2 - metabolism Matrix metalloproteinases Metabolic pathways Metalloproteinase migration Mitogen-Activated Protein Kinase 3 - metabolism Mitogen-Activated Protein Kinases - genetics Mitogen-Activated Protein Kinases - metabolism MMP‐2 Mouth Neoplasms - genetics Mouth Neoplasms - metabolism Mouth Neoplasms - physiopathology Oral cancer Phosphorylation Protein kinase Src protein src-Family Kinases - genetics src-Family Kinases - metabolism Tumor cell lines |
| title | Geraniin inhibits oral cancer cell migration by suppressing matrix metalloproteinase‐2 activation through the FAK/Src and ERK pathways |
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