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4-Hydroxybutenolide impairs cell migration, and invasion of human oral cancer SCC-4 cells via the inhibition of NF-κB and MAPK signaling pathways.

Identifieur interne : 000166 ( Main/Exploration ); précédent : 000165; suivant : 000167

4-Hydroxybutenolide impairs cell migration, and invasion of human oral cancer SCC-4 cells via the inhibition of NF-κB and MAPK signaling pathways.

Auteurs : Fu-Shun Yu [République populaire de Chine] ; Meng-Liang Lin [République populaire de Chine] ; Shu-Chun Hsu [République populaire de Chine] ; Chien-Chih Yu [République populaire de Chine] ; Yi-Ping Huang [République populaire de Chine] ; Yueh-Hsiung Kuo [République populaire de Chine] ; Jing-Gung Chung [République populaire de Chine]

Source :

RBID : pubmed:27221634

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English descriptors

Abstract

4-Hydroxybutenolide (K87), a synthetic compound from furfuryl alcohol via photooxidation, was used to investigate whether it can inhibit mobility, migration and invasion of SCC-4 human oral cancer cells in vitro. Cell viability was measured by flow cytometric assay, the enzymatic activities of MMP-2/9 were assayed by gelatin zymography analysis, the protein levels were assayed by western blotting, confocal laser microscopy and EMSA assay, and the gene expression of MMP-2/-7, FAK and ROCK1 mRNA were assayed by PCR. K87 decreased the percentage of viable cells in dose-dependent manner. K87 suppressed cell mobility, migration and invasion of SCC-4 cells dose-dependently. K87 inhibited the enzymatic activities of MMP-2/9 of SCC-4 cells. Western blot analysis revealed that K87 decreased the protein levels in NF-κBp65, COX-2, ROCK1 and Rho A, MMP-1, -2,- 7, -9, VEGF, GRB2, SOS1, PI3K, PKC, PERK, p-PERK, FAK, MEKK3, MKK7, ERK1/2, JNK1/2, p-p38, p38, p-c-Jun, AKT, TIMP2, but increased the protein levels of iNOS, Ras, IRE-1α, p-c-JNK, p-AKT(308), p-AKT(473) and TIMP1. Results from PCR indicated that K87 inhibited the gene expression of MMP-2/-7, FAK and ROCK1 mRNA. Furthermore, confocal laser microscopy was used to confirm that K87 inhibited the translocation of RHOA and ROCK1 in SCC-4 cells. EMSA assay also show that K87 suppressed the nuclear activation of NF-κB and these effects are time-dependent. Western blotting assay indicated that expression of NF-κBp105, NF-κBp50 and NF-κBp65 proteins were decreased and these effects are time-dependent. Based on these observations, we suggest that K87 may be used as a potential agent for anticancer metastasis of human oral cancer in the future.

DOI: 10.3892/ijo.2016.3537
PubMed: 27221634


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<term>Carcinoma, Squamous Cell (pathology)</term>
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<term>Matrix Metalloproteinase 9 (metabolism)</term>
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<term>Mouth Neoplasms (pathology)</term>
<term>NF-kappa B (antagonists & inhibitors)</term>
<term>NF-kappa B (metabolism)</term>
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<term>Carcinome épidermoïde de la tête et du cou (MeSH)</term>
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<term>Facteur de transcription NF-kappa B (métabolisme)</term>
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<term>Lignée cellulaire tumorale (MeSH)</term>
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<div type="abstract" xml:lang="en">4-Hydroxybutenolide (K87), a synthetic compound from furfuryl alcohol via photooxidation, was used to investigate whether it can inhibit mobility, migration and invasion of SCC-4 human oral cancer cells in vitro. Cell viability was measured by flow cytometric assay, the enzymatic activities of MMP-2/9 were assayed by gelatin zymography analysis, the protein levels were assayed by western blotting, confocal laser microscopy and EMSA assay, and the gene expression of MMP-2/-7, FAK and ROCK1 mRNA were assayed by PCR. K87 decreased the percentage of viable cells in dose-dependent manner. K87 suppressed cell mobility, migration and invasion of SCC-4 cells dose-dependently. K87 inhibited the enzymatic activities of MMP-2/9 of SCC-4 cells. Western blot analysis revealed that K87 decreased the protein levels in NF-κBp65, COX-2, ROCK1 and Rho A, MMP-1, -2,- 7, -9, VEGF, GRB2, SOS1, PI3K, PKC, PERK, p-PERK, FAK, MEKK3, MKK7, ERK1/2, JNK1/2, p-p38, p38, p-c-Jun, AKT, TIMP2, but increased the protein levels of iNOS, Ras, IRE-1α, p-c-JNK, p-AKT(308), p-AKT(473) and TIMP1. Results from PCR indicated that K87 inhibited the gene expression of MMP-2/-7, FAK and ROCK1 mRNA. Furthermore, confocal laser microscopy was used to confirm that K87 inhibited the translocation of RHOA and ROCK1 in SCC-4 cells. EMSA assay also show that K87 suppressed the nuclear activation of NF-κB and these effects are time-dependent. Western blotting assay indicated that expression of NF-κBp105, NF-κBp50 and NF-κBp65 proteins were decreased and these effects are time-dependent. Based on these observations, we suggest that K87 may be used as a potential agent for anticancer metastasis of human oral cancer in the future. </div>
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<AbstractText>4-Hydroxybutenolide (K87), a synthetic compound from furfuryl alcohol via photooxidation, was used to investigate whether it can inhibit mobility, migration and invasion of SCC-4 human oral cancer cells in vitro. Cell viability was measured by flow cytometric assay, the enzymatic activities of MMP-2/9 were assayed by gelatin zymography analysis, the protein levels were assayed by western blotting, confocal laser microscopy and EMSA assay, and the gene expression of MMP-2/-7, FAK and ROCK1 mRNA were assayed by PCR. K87 decreased the percentage of viable cells in dose-dependent manner. K87 suppressed cell mobility, migration and invasion of SCC-4 cells dose-dependently. K87 inhibited the enzymatic activities of MMP-2/9 of SCC-4 cells. Western blot analysis revealed that K87 decreased the protein levels in NF-κBp65, COX-2, ROCK1 and Rho A, MMP-1, -2,- 7, -9, VEGF, GRB2, SOS1, PI3K, PKC, PERK, p-PERK, FAK, MEKK3, MKK7, ERK1/2, JNK1/2, p-p38, p38, p-c-Jun, AKT, TIMP2, but increased the protein levels of iNOS, Ras, IRE-1α, p-c-JNK, p-AKT(308), p-AKT(473) and TIMP1. Results from PCR indicated that K87 inhibited the gene expression of MMP-2/-7, FAK and ROCK1 mRNA. Furthermore, confocal laser microscopy was used to confirm that K87 inhibited the translocation of RHOA and ROCK1 in SCC-4 cells. EMSA assay also show that K87 suppressed the nuclear activation of NF-κB and these effects are time-dependent. Western blotting assay indicated that expression of NF-κBp105, NF-κBp50 and NF-κBp65 proteins were decreased and these effects are time-dependent. Based on these observations, we suggest that K87 may be used as a potential agent for anticancer metastasis of human oral cancer in the future. </AbstractText>
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<NlmUniqueID>9306042</NlmUniqueID>
<ISSNLinking>1019-6439</ISSNLinking>
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<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D061965">Matrix Metalloproteinase Inhibitors</NameOfSubstance>
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<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D016328">NF-kappa B</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>EC 3.4.24.24</RegistryNumber>
<NameOfSubstance UI="C522361">MMP2 protein, human</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>EC 3.4.24.24</RegistryNumber>
<NameOfSubstance UI="D020778">Matrix Metalloproteinase 2</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>EC 3.4.24.35</RegistryNumber>
<NameOfSubstance UI="C579270">MMP9 protein, human</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>EC 3.4.24.35</RegistryNumber>
<NameOfSubstance UI="D020780">Matrix Metalloproteinase 9</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>OL659KIY4X</RegistryNumber>
<NameOfSubstance UI="D015107">4-Butyrolactone</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
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<MeshHeading>
<DescriptorName UI="D015107" MajorTopicYN="N">4-Butyrolactone</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D002294" MajorTopicYN="N">Carcinoma, Squamous Cell</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
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<DescriptorName UI="D045744" MajorTopicYN="N">Cell Line, Tumor</DescriptorName>
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<DescriptorName UI="D002465" MajorTopicYN="N">Cell Movement</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D006258" MajorTopicYN="N">Head and Neck Neoplasms</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D020935" MajorTopicYN="N">MAP Kinase Signaling System</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D020778" MajorTopicYN="N">Matrix Metalloproteinase 2</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D020780" MajorTopicYN="N">Matrix Metalloproteinase 9</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D061965" MajorTopicYN="N">Matrix Metalloproteinase Inhibitors</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D009062" MajorTopicYN="N">Mouth Neoplasms</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D016328" MajorTopicYN="N">NF-kappa B</DescriptorName>
<QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D009361" MajorTopicYN="N">Neoplasm Invasiveness</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000077195" MajorTopicYN="N">Squamous Cell Carcinoma of Head and Neck</DescriptorName>
</MeshHeading>
</MeshHeadingList>
</MedlineCitation>
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<History>
<PubMedPubDate PubStatus="received">
<Year>2016</Year>
<Month>03</Month>
<Day>16</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted">
<Year>2016</Year>
<Month>04</Month>
<Day>27</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez">
<Year>2016</Year>
<Month>5</Month>
<Day>26</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed">
<Year>2016</Year>
<Month>5</Month>
<Day>26</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline">
<Year>2017</Year>
<Month>4</Month>
<Day>26</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList>
<ArticleId IdType="pubmed">27221634</ArticleId>
<ArticleId IdType="doi">10.3892/ijo.2016.3537</ArticleId>
</ArticleIdList>
</PubmedData>
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<affiliations>
<list>
<country>
<li>République populaire de Chine</li>
</country>
</list>
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<country name="République populaire de Chine">
<noRegion>
<name sortKey="Yu, Fu Shun" sort="Yu, Fu Shun" uniqKey="Yu F" first="Fu-Shun" last="Yu">Fu-Shun Yu</name>
</noRegion>
<name sortKey="Chung, Jing Gung" sort="Chung, Jing Gung" uniqKey="Chung J" first="Jing-Gung" last="Chung">Jing-Gung Chung</name>
<name sortKey="Hsu, Shu Chun" sort="Hsu, Shu Chun" uniqKey="Hsu S" first="Shu-Chun" last="Hsu">Shu-Chun Hsu</name>
<name sortKey="Huang, Yi Ping" sort="Huang, Yi Ping" uniqKey="Huang Y" first="Yi-Ping" last="Huang">Yi-Ping Huang</name>
<name sortKey="Kuo, Yueh Hsiung" sort="Kuo, Yueh Hsiung" uniqKey="Kuo Y" first="Yueh-Hsiung" last="Kuo">Yueh-Hsiung Kuo</name>
<name sortKey="Lin, Meng Liang" sort="Lin, Meng Liang" uniqKey="Lin M" first="Meng-Liang" last="Lin">Meng-Liang Lin</name>
<name sortKey="Yu, Chien Chih" sort="Yu, Chien Chih" uniqKey="Yu C" first="Chien-Chih" last="Yu">Chien-Chih Yu</name>
</country>
</tree>
</affiliations>
</record>

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