Norcantharidin, a clinical used chemotherapeutic agent, acts as a powerful inhibitor by interfering with fibrinogen–integrin αIIbβ3 binding in human platelets
During platelet activation, fibrinogen binds to its specific platelet receptor, integrin αIIbβ3, thus completing the final common pathway for platelet aggregation. Norcantharidin (NCTD) is a promising anticancer agent in China from medicinal insect blister beetle. In this study, we provided the evid...
Gespeichert in:
| Veröffentlicht in: | Journal of cellular and molecular medicine 2018-04, Vol.22 (4), p.2142-2152 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2152 |
|---|---|
| container_issue | 4 |
| container_start_page | 2142 |
| container_title | Journal of cellular and molecular medicine |
| container_volume | 22 |
| creator | Hsia, Chih‐Hsuan Lu, Wan‐Jung Lin, Kuan‐Hung Chou, Duen‐Suey Geraldine, Pitchairaj Jayakuma, Thanasekaran Chang, Nen‐Chung Sheu, Joen‐Rong |
| description | During platelet activation, fibrinogen binds to its specific platelet receptor, integrin αIIbβ3, thus completing the final common pathway for platelet aggregation. Norcantharidin (NCTD) is a promising anticancer agent in China from medicinal insect blister beetle. In this study, we provided the evidence to demonstrate NCTD (0.1–1.0 μM) possesses very powerful antiplatelet activity in human platelets; nevertheless, it had no effects on surface P‐selectin expression and only slight inhibition on ATP‐release reaction in activated platelets. Moreover, NCTD markedly hindered integrin αIIbβ3 activation by interfering with the binding of FITC‐labelled PAC‐1. It also markedly reduced the number of adherent platelets and the single platelet spreading area on immobilized fibrinogen as well as clot retraction. Additionally, NCTD attenuated phosphorylation of proteins such as integrin β3, Src and FAK in platelets spreading on immobilized fibrinogen. These results indicate that NCTD restricts integrin αIIbβ3‐mediated outside‐in signalling in human platelets. Besides, NCTD substantially prolonged the closure time in human whole blood and increased the occlusion time of thrombotic platelet plug formation and prolonged the bleeding time in mice. In conclusion, NCTD has dual activities, it can be a chemotherapeutic agent for cancer treatment, and the other side it possesses powerful antiplatelet activity for treating thromboembolic disorders. |
| doi_str_mv | 10.1111/jcmm.13488 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_wiley</sourceid><recordid>TN_cdi_proquest_miscellaneous_1991186202</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2017685773</sourcerecordid><originalsourceid>FETCH-LOGICAL-p1398-4f69910ff4ab412354700f667f77c0a9f16df20c92d7d1b4fdc8916484962a413</originalsourceid><addsrcrecordid>eNpdkU1u2zAQhYUiAeok3fQEBLrpIk44Ik1Ry8JIGhf52bRrgqJIiwZFqSQFw7vcITfoDdKD-BA9SekkqxADcN7wm8EQryg-A76AfC43qu8vgFDOPxQzWPByTmtCj95y4IR_LE5i3GBMGJB6Vvy5H4KSPnUy2Nb6cySRctZbJR2aom6R6nQ_pE4HOeopWYXkWvuUOZUikjnQOGx1MJND1ne2sWkIqNllkXJVB-vXaGtTh4xtshhy97_Hp8PrOku0f16tmv1fghrr2wOba93US49GJ5N2OsWz4thIF_Wnt_u0-HV99XN5M799-L5afrudj_knfE4Nq2vAxlDZUCjJglYYG8YqU1UKy9oAa02JVV22VQsNNa3iNTDKac1KSYGcFl9f545h-D3pmERvo9LOSa-HKQrI44GzEpcZ_fIO3QxT8Hk7UWKoGF9UFckUvFJb6_ROjMH2MuwEYHHwShy8Ei9eiR_Lu7uXjPwHwPOOSw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2017685773</pqid></control><display><type>article</type><title>Norcantharidin, a clinical used chemotherapeutic agent, acts as a powerful inhibitor by interfering with fibrinogen–integrin αIIbβ3 binding in human platelets</title><source>DOAJ Directory of Open Access Journals</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Wiley-Blackwell Open Access Titles</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Hsia, Chih‐Hsuan ; Lu, Wan‐Jung ; Lin, Kuan‐Hung ; Chou, Duen‐Suey ; Geraldine, Pitchairaj ; Jayakuma, Thanasekaran ; Chang, Nen‐Chung ; Sheu, Joen‐Rong</creator><creatorcontrib>Hsia, Chih‐Hsuan ; Lu, Wan‐Jung ; Lin, Kuan‐Hung ; Chou, Duen‐Suey ; Geraldine, Pitchairaj ; Jayakuma, Thanasekaran ; Chang, Nen‐Chung ; Sheu, Joen‐Rong</creatorcontrib><description>During platelet activation, fibrinogen binds to its specific platelet receptor, integrin αIIbβ3, thus completing the final common pathway for platelet aggregation. Norcantharidin (NCTD) is a promising anticancer agent in China from medicinal insect blister beetle. In this study, we provided the evidence to demonstrate NCTD (0.1–1.0 μM) possesses very powerful antiplatelet activity in human platelets; nevertheless, it had no effects on surface P‐selectin expression and only slight inhibition on ATP‐release reaction in activated platelets. Moreover, NCTD markedly hindered integrin αIIbβ3 activation by interfering with the binding of FITC‐labelled PAC‐1. It also markedly reduced the number of adherent platelets and the single platelet spreading area on immobilized fibrinogen as well as clot retraction. Additionally, NCTD attenuated phosphorylation of proteins such as integrin β3, Src and FAK in platelets spreading on immobilized fibrinogen. These results indicate that NCTD restricts integrin αIIbβ3‐mediated outside‐in signalling in human platelets. Besides, NCTD substantially prolonged the closure time in human whole blood and increased the occlusion time of thrombotic platelet plug formation and prolonged the bleeding time in mice. In conclusion, NCTD has dual activities, it can be a chemotherapeutic agent for cancer treatment, and the other side it possesses powerful antiplatelet activity for treating thromboembolic disorders.</description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/jcmm.13488</identifier><language>eng</language><publisher>Chichester: John Wiley & Sons, Inc</publisher><subject>Activation ; antithrombosis ; Blistering ; Cancer ; Chemotherapy ; Fibrinogen ; Focal adhesion kinase ; integrin αIIbβ3 ; Norcantharidin ; Occlusion ; Phosphorylation ; Platelet aggregation ; Proteins ; Signal transduction ; Spreading ; Thromboembolism</subject><ispartof>Journal of cellular and molecular medicine, 2018-04, Vol.22 (4), p.2142-2152</ispartof><rights>2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.</rights><rights>2018. This work is published under https://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0002-3999-9507</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjcmm.13488$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjcmm.13488$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,864,1416,11553,27915,27916,45565,45566,46043,46467</link.rule.ids></links><search><creatorcontrib>Hsia, Chih‐Hsuan</creatorcontrib><creatorcontrib>Lu, Wan‐Jung</creatorcontrib><creatorcontrib>Lin, Kuan‐Hung</creatorcontrib><creatorcontrib>Chou, Duen‐Suey</creatorcontrib><creatorcontrib>Geraldine, Pitchairaj</creatorcontrib><creatorcontrib>Jayakuma, Thanasekaran</creatorcontrib><creatorcontrib>Chang, Nen‐Chung</creatorcontrib><creatorcontrib>Sheu, Joen‐Rong</creatorcontrib><title>Norcantharidin, a clinical used chemotherapeutic agent, acts as a powerful inhibitor by interfering with fibrinogen–integrin αIIbβ3 binding in human platelets</title><title>Journal of cellular and molecular medicine</title><description>During platelet activation, fibrinogen binds to its specific platelet receptor, integrin αIIbβ3, thus completing the final common pathway for platelet aggregation. Norcantharidin (NCTD) is a promising anticancer agent in China from medicinal insect blister beetle. In this study, we provided the evidence to demonstrate NCTD (0.1–1.0 μM) possesses very powerful antiplatelet activity in human platelets; nevertheless, it had no effects on surface P‐selectin expression and only slight inhibition on ATP‐release reaction in activated platelets. Moreover, NCTD markedly hindered integrin αIIbβ3 activation by interfering with the binding of FITC‐labelled PAC‐1. It also markedly reduced the number of adherent platelets and the single platelet spreading area on immobilized fibrinogen as well as clot retraction. Additionally, NCTD attenuated phosphorylation of proteins such as integrin β3, Src and FAK in platelets spreading on immobilized fibrinogen. These results indicate that NCTD restricts integrin αIIbβ3‐mediated outside‐in signalling in human platelets. Besides, NCTD substantially prolonged the closure time in human whole blood and increased the occlusion time of thrombotic platelet plug formation and prolonged the bleeding time in mice. In conclusion, NCTD has dual activities, it can be a chemotherapeutic agent for cancer treatment, and the other side it possesses powerful antiplatelet activity for treating thromboembolic disorders.</description><subject>Activation</subject><subject>antithrombosis</subject><subject>Blistering</subject><subject>Cancer</subject><subject>Chemotherapy</subject><subject>Fibrinogen</subject><subject>Focal adhesion kinase</subject><subject>integrin αIIbβ3</subject><subject>Norcantharidin</subject><subject>Occlusion</subject><subject>Phosphorylation</subject><subject>Platelet aggregation</subject><subject>Proteins</subject><subject>Signal transduction</subject><subject>Spreading</subject><subject>Thromboembolism</subject><issn>1582-1838</issn><issn>1582-4934</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpdkU1u2zAQhYUiAeok3fQEBLrpIk44Ik1Ry8JIGhf52bRrgqJIiwZFqSQFw7vcITfoDdKD-BA9SekkqxADcN7wm8EQryg-A76AfC43qu8vgFDOPxQzWPByTmtCj95y4IR_LE5i3GBMGJB6Vvy5H4KSPnUy2Nb6cySRctZbJR2aom6R6nQ_pE4HOeopWYXkWvuUOZUikjnQOGx1MJND1ne2sWkIqNllkXJVB-vXaGtTh4xtshhy97_Hp8PrOku0f16tmv1fghrr2wOba93US49GJ5N2OsWz4thIF_Wnt_u0-HV99XN5M799-L5afrudj_knfE4Nq2vAxlDZUCjJglYYG8YqU1UKy9oAa02JVV22VQsNNa3iNTDKac1KSYGcFl9f545h-D3pmERvo9LOSa-HKQrI44GzEpcZ_fIO3QxT8Hk7UWKoGF9UFckUvFJb6_ROjMH2MuwEYHHwShy8Ei9eiR_Lu7uXjPwHwPOOSw</recordid><startdate>201804</startdate><enddate>201804</enddate><creator>Hsia, Chih‐Hsuan</creator><creator>Lu, Wan‐Jung</creator><creator>Lin, Kuan‐Hung</creator><creator>Chou, Duen‐Suey</creator><creator>Geraldine, Pitchairaj</creator><creator>Jayakuma, Thanasekaran</creator><creator>Chang, Nen‐Chung</creator><creator>Sheu, Joen‐Rong</creator><general>John Wiley & Sons, Inc</general><scope>24P</scope><scope>WIN</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3999-9507</orcidid></search><sort><creationdate>201804</creationdate><title>Norcantharidin, a clinical used chemotherapeutic agent, acts as a powerful inhibitor by interfering with fibrinogen–integrin αIIbβ3 binding in human platelets</title><author>Hsia, Chih‐Hsuan ; Lu, Wan‐Jung ; Lin, Kuan‐Hung ; Chou, Duen‐Suey ; Geraldine, Pitchairaj ; Jayakuma, Thanasekaran ; Chang, Nen‐Chung ; Sheu, Joen‐Rong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p1398-4f69910ff4ab412354700f667f77c0a9f16df20c92d7d1b4fdc8916484962a413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Activation</topic><topic>antithrombosis</topic><topic>Blistering</topic><topic>Cancer</topic><topic>Chemotherapy</topic><topic>Fibrinogen</topic><topic>Focal adhesion kinase</topic><topic>integrin αIIbβ3</topic><topic>Norcantharidin</topic><topic>Occlusion</topic><topic>Phosphorylation</topic><topic>Platelet aggregation</topic><topic>Proteins</topic><topic>Signal transduction</topic><topic>Spreading</topic><topic>Thromboembolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hsia, Chih‐Hsuan</creatorcontrib><creatorcontrib>Lu, Wan‐Jung</creatorcontrib><creatorcontrib>Lin, Kuan‐Hung</creatorcontrib><creatorcontrib>Chou, Duen‐Suey</creatorcontrib><creatorcontrib>Geraldine, Pitchairaj</creatorcontrib><creatorcontrib>Jayakuma, Thanasekaran</creatorcontrib><creatorcontrib>Chang, Nen‐Chung</creatorcontrib><creatorcontrib>Sheu, Joen‐Rong</creatorcontrib><collection>Wiley-Blackwell Open Access Titles</collection><collection>Wiley Online Library Free Content</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech 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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</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>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database (ProQuest)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</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 Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cellular and molecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hsia, Chih‐Hsuan</au><au>Lu, Wan‐Jung</au><au>Lin, Kuan‐Hung</au><au>Chou, Duen‐Suey</au><au>Geraldine, Pitchairaj</au><au>Jayakuma, Thanasekaran</au><au>Chang, Nen‐Chung</au><au>Sheu, Joen‐Rong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Norcantharidin, a clinical used chemotherapeutic agent, acts as a powerful inhibitor by interfering with fibrinogen–integrin αIIbβ3 binding in human platelets</atitle><jtitle>Journal of cellular and molecular medicine</jtitle><date>2018-04</date><risdate>2018</risdate><volume>22</volume><issue>4</issue><spage>2142</spage><epage>2152</epage><pages>2142-2152</pages><issn>1582-1838</issn><eissn>1582-4934</eissn><abstract>During platelet activation, fibrinogen binds to its specific platelet receptor, integrin αIIbβ3, thus completing the final common pathway for platelet aggregation. Norcantharidin (NCTD) is a promising anticancer agent in China from medicinal insect blister beetle. In this study, we provided the evidence to demonstrate NCTD (0.1–1.0 μM) possesses very powerful antiplatelet activity in human platelets; nevertheless, it had no effects on surface P‐selectin expression and only slight inhibition on ATP‐release reaction in activated platelets. Moreover, NCTD markedly hindered integrin αIIbβ3 activation by interfering with the binding of FITC‐labelled PAC‐1. It also markedly reduced the number of adherent platelets and the single platelet spreading area on immobilized fibrinogen as well as clot retraction. Additionally, NCTD attenuated phosphorylation of proteins such as integrin β3, Src and FAK in platelets spreading on immobilized fibrinogen. These results indicate that NCTD restricts integrin αIIbβ3‐mediated outside‐in signalling in human platelets. Besides, NCTD substantially prolonged the closure time in human whole blood and increased the occlusion time of thrombotic platelet plug formation and prolonged the bleeding time in mice. In conclusion, NCTD has dual activities, it can be a chemotherapeutic agent for cancer treatment, and the other side it possesses powerful antiplatelet activity for treating thromboembolic disorders.</abstract><cop>Chichester</cop><pub>John Wiley & Sons, Inc</pub><doi>10.1111/jcmm.13488</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-3999-9507</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1582-1838 |
| ispartof | Journal of cellular and molecular medicine, 2018-04, Vol.22 (4), p.2142-2152 |
| issn | 1582-1838 1582-4934 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1991186202 |
| source | DOAJ Directory of Open Access Journals; Wiley Online Library Journals Frontfile Complete; Wiley-Blackwell Open Access Titles; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Activation antithrombosis Blistering Cancer Chemotherapy Fibrinogen Focal adhesion kinase integrin αIIbβ3 Norcantharidin Occlusion Phosphorylation Platelet aggregation Proteins Signal transduction Spreading Thromboembolism |
| title | Norcantharidin, a clinical used chemotherapeutic agent, acts as a powerful inhibitor by interfering with fibrinogen–integrin αIIbβ3 binding in human platelets |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T01%3A56%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_wiley&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Norcantharidin,%20a%20clinical%20used%20chemotherapeutic%20agent,%20acts%20as%20a%20powerful%20inhibitor%20by%20interfering%20with%20fibrinogen%E2%80%93integrin%20%CE%B1IIb%CE%B23%20binding%20in%20human%20platelets&rft.jtitle=Journal%20of%20cellular%20and%20molecular%20medicine&rft.au=Hsia,%20Chih%E2%80%90Hsuan&rft.date=2018-04&rft.volume=22&rft.issue=4&rft.spage=2142&rft.epage=2152&rft.pages=2142-2152&rft.issn=1582-1838&rft.eissn=1582-4934&rft_id=info:doi/10.1111/jcmm.13488&rft_dat=%3Cproquest_wiley%3E2017685773%3C/proquest_wiley%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2017685773&rft_id=info:pmid/&rfr_iscdi=true |