Cordycepin Induces Apoptosis of CGTH W-2 Thyroid Carcinoma Cells through the Calcium−Calpain−Caspase 7-PARP Pathway
Cordycepin, a nucleoside isolated from Cordyceps sinensis, is an inhibitor of polyadenylation and has an antitumor effect. We used CGTH W-2, a follicular thyroid carcinoma cell line, to study the mechanism of the anticancer effect of cordycepin. Cordycepin decreased cell viability and resulted in ap...
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| Veröffentlicht in: | Journal of agricultural and food chemistry 2010-11, Vol.58 (22), p.11645-11652 |
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| creator | Chen, Ying Chen, Yung-Chia Lin, Yen-Tung Huang, Shih-Horng Wang, Seu-Mei |
| description | Cordycepin, a nucleoside isolated from Cordyceps sinensis, is an inhibitor of polyadenylation and has an antitumor effect. We used CGTH W-2, a follicular thyroid carcinoma cell line, to study the mechanism of the anticancer effect of cordycepin. Cordycepin decreased cell viability and resulted in apoptosis but not necrosis. Cordycepin increased intracellular calcium levels triggering calpain activation, which led to apoptosis. BAPTA/AM and calpeptin inhibited the cordycepin-induced cleavage of caspase 7 and poly (ADP-ribose) polymerase (PARP), implying an upstream role of calcium and calpain. CGTH W-2 cells expressed four subtypes of adenosine receptors (AR), A1AR, A2AAR, A2BAR, and A3AR. Specific antagonists to AR subtypes all blocked cordycepin-induced apoptosis to different degrees. Small interfering RNA for A1AR and A3AR abrogated cordycepin-induced apoptosis. In conclusion, the cordycepin-induced apoptosis of CGTH W-2 cells is mediated by the calcium−calpain−caspase 7-PARP pathway, and ARs are involved in the apoptotic effect of cordycepin. |
| doi_str_mv | 10.1021/jf1028976 |
| format | Article |
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We used CGTH W-2, a follicular thyroid carcinoma cell line, to study the mechanism of the anticancer effect of cordycepin. Cordycepin decreased cell viability and resulted in apoptosis but not necrosis. Cordycepin increased intracellular calcium levels triggering calpain activation, which led to apoptosis. BAPTA/AM and calpeptin inhibited the cordycepin-induced cleavage of caspase 7 and poly (ADP-ribose) polymerase (PARP), implying an upstream role of calcium and calpain. CGTH W-2 cells expressed four subtypes of adenosine receptors (AR), A1AR, A2AAR, A2BAR, and A3AR. Specific antagonists to AR subtypes all blocked cordycepin-induced apoptosis to different degrees. Small interfering RNA for A1AR and A3AR abrogated cordycepin-induced apoptosis. In conclusion, the cordycepin-induced apoptosis of CGTH W-2 cells is mediated by the calcium−calpain−caspase 7-PARP pathway, and ARs are involved in the apoptotic effect of cordycepin.</description><identifier>ISSN: 0021-8561</identifier><identifier>EISSN: 1520-5118</identifier><identifier>DOI: 10.1021/jf1028976</identifier><identifier>PMID: 20961042</identifier><identifier>CODEN: JAFCAU</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>anticarcinogenic activity ; Antineoplastic Agents, Phytogenic - pharmacology ; apoptosis ; Apoptosis - drug effects ; Bioactive Constituents ; biochemical pathways ; Biological and medical sciences ; calcium ; Calcium - metabolism ; calpain ; Calpain - genetics ; Calpain - metabolism ; carcinoma ; Caspase 7 - genetics ; Caspase 7 - metabolism ; caspases ; cell culture ; Cell Line, Tumor ; cordycepin ; Cordyceps ; Cordyceps - chemistry ; Deoxyadenosines - pharmacology ; Food industries ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation, Neoplastic - drug effects ; human cell lines ; Humans ; medicinal plants ; neoplasms ; Poly(ADP-ribose) Polymerases - genetics ; Poly(ADP-ribose) Polymerases - metabolism ; Signal Transduction - drug effects ; thyroid diseases ; Thyroid Neoplasms - drug therapy ; Thyroid Neoplasms - genetics ; Thyroid Neoplasms - metabolism ; Thyroid Neoplasms - physiopathology ; traditional medicine</subject><ispartof>Journal of agricultural and food chemistry, 2010-11, Vol.58 (22), p.11645-11652</ispartof><rights>Copyright © 2010 American Chemical Society</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a434t-e614f5e718f477c2d2affd05a672b51febe82887a46af56f036d920f36c7614a3</citedby><cites>FETCH-LOGICAL-a434t-e614f5e718f477c2d2affd05a672b51febe82887a46af56f036d920f36c7614a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jf1028976$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jf1028976$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23463282$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20961042$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Ying</creatorcontrib><creatorcontrib>Chen, Yung-Chia</creatorcontrib><creatorcontrib>Lin, Yen-Tung</creatorcontrib><creatorcontrib>Huang, Shih-Horng</creatorcontrib><creatorcontrib>Wang, Seu-Mei</creatorcontrib><title>Cordycepin Induces Apoptosis of CGTH W-2 Thyroid Carcinoma Cells through the Calcium−Calpain−Caspase 7-PARP Pathway</title><title>Journal of agricultural and food chemistry</title><addtitle>J. Agric. Food Chem</addtitle><description>Cordycepin, a nucleoside isolated from Cordyceps sinensis, is an inhibitor of polyadenylation and has an antitumor effect. We used CGTH W-2, a follicular thyroid carcinoma cell line, to study the mechanism of the anticancer effect of cordycepin. Cordycepin decreased cell viability and resulted in apoptosis but not necrosis. Cordycepin increased intracellular calcium levels triggering calpain activation, which led to apoptosis. BAPTA/AM and calpeptin inhibited the cordycepin-induced cleavage of caspase 7 and poly (ADP-ribose) polymerase (PARP), implying an upstream role of calcium and calpain. CGTH W-2 cells expressed four subtypes of adenosine receptors (AR), A1AR, A2AAR, A2BAR, and A3AR. Specific antagonists to AR subtypes all blocked cordycepin-induced apoptosis to different degrees. Small interfering RNA for A1AR and A3AR abrogated cordycepin-induced apoptosis. In conclusion, the cordycepin-induced apoptosis of CGTH W-2 cells is mediated by the calcium−calpain−caspase 7-PARP pathway, and ARs are involved in the apoptotic effect of cordycepin.</description><subject>anticarcinogenic activity</subject><subject>Antineoplastic Agents, Phytogenic - pharmacology</subject><subject>apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Bioactive Constituents</subject><subject>biochemical pathways</subject><subject>Biological and medical sciences</subject><subject>calcium</subject><subject>Calcium - metabolism</subject><subject>calpain</subject><subject>Calpain - genetics</subject><subject>Calpain - metabolism</subject><subject>carcinoma</subject><subject>Caspase 7 - genetics</subject><subject>Caspase 7 - metabolism</subject><subject>caspases</subject><subject>cell culture</subject><subject>Cell Line, Tumor</subject><subject>cordycepin</subject><subject>Cordyceps</subject><subject>Cordyceps - chemistry</subject><subject>Deoxyadenosines - pharmacology</subject><subject>Food industries</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>human cell lines</subject><subject>Humans</subject><subject>medicinal plants</subject><subject>neoplasms</subject><subject>Poly(ADP-ribose) Polymerases - genetics</subject><subject>Poly(ADP-ribose) Polymerases - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>thyroid diseases</subject><subject>Thyroid Neoplasms - drug therapy</subject><subject>Thyroid Neoplasms - genetics</subject><subject>Thyroid Neoplasms - metabolism</subject><subject>Thyroid Neoplasms - physiopathology</subject><subject>traditional medicine</subject><issn>0021-8561</issn><issn>1520-5118</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkM1u1DAUhS1ERYfCghcAbyrEImA7_pvlKKI_UqWOYCqW0R3H7niUxMFOVM0bsO4j8iS4zLTddHWOdL97dO9B6AMlXylh9NvWZdFzJV-hGRWMFIJS_RrNSB4WWkh6jN6mtCWEaKHIG3TMyFxSwtkM3VUhNjtjB9_jy76ZjE14MYRhDMknHByuzlcX-FfB8Gqzi8E3uIJofB86wJVt24THTQzT7SarzbPW-Kn7--c-uwF8_9-lAZLFqlgufizxEsbNHezeoSMHbbLvD3qCbs6-r6qL4ur6_LJaXBXASz4WVlLuhFVUO66UYQ0D5xoiQCq2FtTZtdVMawVcghPSkVI2c0ZcKY3Kq1CeoM_73CGG35NNY935ZPLh0NswpVoTzSXjpczklz1pYkgpWlcP0XcQdzUl9UPN9VPNmf14SJ3WnW2eyMdeM3B6ACAZaF2E3vj0zJVclkw_cJ_2nINQw23MzM1PRmhJaH5DMPWcBCbV2zDFPtf1wkn_AMQ0mi4</recordid><startdate>20101124</startdate><enddate>20101124</enddate><creator>Chen, Ying</creator><creator>Chen, Yung-Chia</creator><creator>Lin, Yen-Tung</creator><creator>Huang, Shih-Horng</creator><creator>Wang, Seu-Mei</creator><general>American Chemical Society</general><scope>FBQ</scope><scope>IQODW</scope><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></search><sort><creationdate>20101124</creationdate><title>Cordycepin Induces Apoptosis of CGTH W-2 Thyroid Carcinoma Cells through the Calcium−Calpain−Caspase 7-PARP Pathway</title><author>Chen, Ying ; Chen, Yung-Chia ; Lin, Yen-Tung ; Huang, Shih-Horng ; Wang, Seu-Mei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a434t-e614f5e718f477c2d2affd05a672b51febe82887a46af56f036d920f36c7614a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>anticarcinogenic activity</topic><topic>Antineoplastic Agents, Phytogenic - pharmacology</topic><topic>apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Bioactive Constituents</topic><topic>biochemical pathways</topic><topic>Biological and medical sciences</topic><topic>calcium</topic><topic>Calcium - metabolism</topic><topic>calpain</topic><topic>Calpain - genetics</topic><topic>Calpain - metabolism</topic><topic>carcinoma</topic><topic>Caspase 7 - genetics</topic><topic>Caspase 7 - metabolism</topic><topic>caspases</topic><topic>cell culture</topic><topic>Cell Line, Tumor</topic><topic>cordycepin</topic><topic>Cordyceps</topic><topic>Cordyceps - chemistry</topic><topic>Deoxyadenosines - pharmacology</topic><topic>Food industries</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>human cell lines</topic><topic>Humans</topic><topic>medicinal plants</topic><topic>neoplasms</topic><topic>Poly(ADP-ribose) Polymerases - genetics</topic><topic>Poly(ADP-ribose) Polymerases - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>thyroid diseases</topic><topic>Thyroid Neoplasms - drug therapy</topic><topic>Thyroid Neoplasms - genetics</topic><topic>Thyroid Neoplasms - metabolism</topic><topic>Thyroid Neoplasms - physiopathology</topic><topic>traditional medicine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Ying</creatorcontrib><creatorcontrib>Chen, Yung-Chia</creatorcontrib><creatorcontrib>Lin, Yen-Tung</creatorcontrib><creatorcontrib>Huang, Shih-Horng</creatorcontrib><creatorcontrib>Wang, Seu-Mei</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><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><jtitle>Journal of agricultural and food chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Ying</au><au>Chen, Yung-Chia</au><au>Lin, Yen-Tung</au><au>Huang, Shih-Horng</au><au>Wang, Seu-Mei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cordycepin Induces Apoptosis of CGTH W-2 Thyroid Carcinoma Cells through the Calcium−Calpain−Caspase 7-PARP Pathway</atitle><jtitle>Journal of agricultural and food chemistry</jtitle><addtitle>J. Agric. Food Chem</addtitle><date>2010-11-24</date><risdate>2010</risdate><volume>58</volume><issue>22</issue><spage>11645</spage><epage>11652</epage><pages>11645-11652</pages><issn>0021-8561</issn><eissn>1520-5118</eissn><coden>JAFCAU</coden><abstract>Cordycepin, a nucleoside isolated from Cordyceps sinensis, is an inhibitor of polyadenylation and has an antitumor effect. We used CGTH W-2, a follicular thyroid carcinoma cell line, to study the mechanism of the anticancer effect of cordycepin. Cordycepin decreased cell viability and resulted in apoptosis but not necrosis. Cordycepin increased intracellular calcium levels triggering calpain activation, which led to apoptosis. BAPTA/AM and calpeptin inhibited the cordycepin-induced cleavage of caspase 7 and poly (ADP-ribose) polymerase (PARP), implying an upstream role of calcium and calpain. CGTH W-2 cells expressed four subtypes of adenosine receptors (AR), A1AR, A2AAR, A2BAR, and A3AR. Specific antagonists to AR subtypes all blocked cordycepin-induced apoptosis to different degrees. Small interfering RNA for A1AR and A3AR abrogated cordycepin-induced apoptosis. In conclusion, the cordycepin-induced apoptosis of CGTH W-2 cells is mediated by the calcium−calpain−caspase 7-PARP pathway, and ARs are involved in the apoptotic effect of cordycepin.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>20961042</pmid><doi>10.1021/jf1028976</doi><tpages>8</tpages></addata></record> |
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| subjects | anticarcinogenic activity Antineoplastic Agents, Phytogenic - pharmacology apoptosis Apoptosis - drug effects Bioactive Constituents biochemical pathways Biological and medical sciences calcium Calcium - metabolism calpain Calpain - genetics Calpain - metabolism carcinoma Caspase 7 - genetics Caspase 7 - metabolism caspases cell culture Cell Line, Tumor cordycepin Cordyceps Cordyceps - chemistry Deoxyadenosines - pharmacology Food industries Fundamental and applied biological sciences. Psychology Gene Expression Regulation, Neoplastic - drug effects human cell lines Humans medicinal plants neoplasms Poly(ADP-ribose) Polymerases - genetics Poly(ADP-ribose) Polymerases - metabolism Signal Transduction - drug effects thyroid diseases Thyroid Neoplasms - drug therapy Thyroid Neoplasms - genetics Thyroid Neoplasms - metabolism Thyroid Neoplasms - physiopathology traditional medicine |
| title | Cordycepin Induces Apoptosis of CGTH W-2 Thyroid Carcinoma Cells through the Calcium−Calpain−Caspase 7-PARP Pathway |
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