Cordycepin induces apoptosis by caveolin-1-mediated JNK regulation of Foxo3a in human lung adenocarcinoma
Forkhead transcription factor (Foxo3a) is a downstream effector of JNK-induced tumor suppression. However, it is not clear whether the caveolin-1 (CAV1)-mediated JNK/Foxo3a pathway is involved in cancer cell apoptosis. We found that cordycepin upregulates CAV1 expression, which was accompanied by JN...
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| creator | Joo, Jong Cheon Hwang, Jung Hoo Jo, Eunbi Kim, Young-Rang Kim, Dae Joon Lee, Kyung-Bok Park, Soo Jung Jang, Ik-Soon |
| description | Forkhead transcription factor (Foxo3a) is a downstream effector of JNK-induced tumor suppression. However, it is not clear whether the caveolin-1 (CAV1)-mediated JNK/Foxo3a pathway is involved in cancer cell apoptosis. We found that cordycepin upregulates CAV1 expression, which was accompanied by JNK phosphorylation (p-JNK) and subsequent Foxo3a translocation into the nucleus, resulting in the upregulation of Bax protein expression. Furthermore, we found that CAV1 overexpression upregulated p-JNK, whereas CAV1 siRNA downregulated p-JNK. Additionally, SP600125, a specific JNK inhibitor, significantly increased Foxo3a phosphorylation, which downregulated Foxo3a translocation into the nucleus, indicating that CAV1 mediates JNK regulation of Foxo3a. Foxo3a siRNA downregulated Bax protein and attenuated A549 apoptosis, indicating that the CAV1-mediated JNK/Foxo3a pathway induces the apoptosis of A549 lung cancer cells. Cordycepin significantly decreased tumor volume in nude mice. Taken together, these results indicate that cordycepin promotes CAV1 upregulation to enhance JNK/Foxo3a signaling pathway activation, inducing apoptosis in lung cancer cells, and support its potential as a therapeutic agent for lung cancer. |
| doi_str_mv | 10.18632/oncotarget.14661 |
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However, it is not clear whether the caveolin-1 (CAV1)-mediated JNK/Foxo3a pathway is involved in cancer cell apoptosis. We found that cordycepin upregulates CAV1 expression, which was accompanied by JNK phosphorylation (p-JNK) and subsequent Foxo3a translocation into the nucleus, resulting in the upregulation of Bax protein expression. Furthermore, we found that CAV1 overexpression upregulated p-JNK, whereas CAV1 siRNA downregulated p-JNK. Additionally, SP600125, a specific JNK inhibitor, significantly increased Foxo3a phosphorylation, which downregulated Foxo3a translocation into the nucleus, indicating that CAV1 mediates JNK regulation of Foxo3a. Foxo3a siRNA downregulated Bax protein and attenuated A549 apoptosis, indicating that the CAV1-mediated JNK/Foxo3a pathway induces the apoptosis of A549 lung cancer cells. Cordycepin significantly decreased tumor volume in nude mice. Taken together, these results indicate that cordycepin promotes CAV1 upregulation to enhance JNK/Foxo3a signaling pathway activation, inducing apoptosis in lung cancer cells, and support its potential as a therapeutic agent for lung cancer.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.14661</identifier><identifier>PMID: 28099944</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>A549 Cells ; Adenocarcinoma - drug therapy ; Adenocarcinoma - genetics ; Adenocarcinoma - metabolism ; Animals ; Anthracenes - pharmacology ; Apoptosis - drug effects ; Apoptosis - genetics ; Blotting, Western ; Caveolin 1 - genetics ; Caveolin 1 - metabolism ; Cell Line, Tumor ; Deoxyadenosines - pharmacology ; Forkhead Box Protein O3 - genetics ; Forkhead Box Protein O3 - metabolism ; Gene Expression Profiling - methods ; Gene Expression Regulation, Neoplastic - drug effects ; Gene Ontology ; Gene Regulatory Networks ; Humans ; JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors ; JNK Mitogen-Activated Protein Kinases - genetics ; JNK Mitogen-Activated Protein Kinases - metabolism ; Lung Neoplasms - drug therapy ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Mice, Inbred BALB C ; Mice, Nude ; Microscopy, Fluorescence ; Phosphorylation - drug effects ; Research Paper ; RNA Interference ; Signal Transduction - drug effects ; Signal Transduction - genetics ; Xenograft Model Antitumor Assays</subject><ispartof>Oncotarget, 2017-02, Vol.8 (7), p.12211-12224</ispartof><rights>Copyright: © 2017 Joo et al. 2017</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-304925fac5d474ce21ba459aae31ab33bc93ce0893ce2c6c91bbdff41ba8cc7f3</citedby><cites>FETCH-LOGICAL-c356t-304925fac5d474ce21ba459aae31ab33bc93ce0893ce2c6c91bbdff41ba8cc7f3</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/PMC5355338/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355338/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28099944$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Joo, Jong Cheon</creatorcontrib><creatorcontrib>Hwang, Jung Hoo</creatorcontrib><creatorcontrib>Jo, Eunbi</creatorcontrib><creatorcontrib>Kim, Young-Rang</creatorcontrib><creatorcontrib>Kim, Dae Joon</creatorcontrib><creatorcontrib>Lee, Kyung-Bok</creatorcontrib><creatorcontrib>Park, Soo Jung</creatorcontrib><creatorcontrib>Jang, Ik-Soon</creatorcontrib><title>Cordycepin induces apoptosis by caveolin-1-mediated JNK regulation of Foxo3a in human lung adenocarcinoma</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>Forkhead transcription factor (Foxo3a) is a downstream effector of JNK-induced tumor suppression. However, it is not clear whether the caveolin-1 (CAV1)-mediated JNK/Foxo3a pathway is involved in cancer cell apoptosis. We found that cordycepin upregulates CAV1 expression, which was accompanied by JNK phosphorylation (p-JNK) and subsequent Foxo3a translocation into the nucleus, resulting in the upregulation of Bax protein expression. Furthermore, we found that CAV1 overexpression upregulated p-JNK, whereas CAV1 siRNA downregulated p-JNK. Additionally, SP600125, a specific JNK inhibitor, significantly increased Foxo3a phosphorylation, which downregulated Foxo3a translocation into the nucleus, indicating that CAV1 mediates JNK regulation of Foxo3a. Foxo3a siRNA downregulated Bax protein and attenuated A549 apoptosis, indicating that the CAV1-mediated JNK/Foxo3a pathway induces the apoptosis of A549 lung cancer cells. Cordycepin significantly decreased tumor volume in nude mice. Taken together, these results indicate that cordycepin promotes CAV1 upregulation to enhance JNK/Foxo3a signaling pathway activation, inducing apoptosis in lung cancer cells, and support its potential as a therapeutic agent for lung cancer.</description><subject>A549 Cells</subject><subject>Adenocarcinoma - drug therapy</subject><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - metabolism</subject><subject>Animals</subject><subject>Anthracenes - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - genetics</subject><subject>Blotting, Western</subject><subject>Caveolin 1 - genetics</subject><subject>Caveolin 1 - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Deoxyadenosines - pharmacology</subject><subject>Forkhead Box Protein O3 - genetics</subject><subject>Forkhead Box Protein O3 - metabolism</subject><subject>Gene Expression Profiling - methods</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Gene Ontology</subject><subject>Gene Regulatory Networks</subject><subject>Humans</subject><subject>JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors</subject><subject>JNK Mitogen-Activated Protein Kinases - genetics</subject><subject>JNK Mitogen-Activated Protein Kinases - metabolism</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Microscopy, Fluorescence</subject><subject>Phosphorylation - drug effects</subject><subject>Research Paper</subject><subject>RNA Interference</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - genetics</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUUFP3jAMjSYQIMYP4IJy3KWsaZJ-zQVp-gSDDY0LnCPXTT-C2rgkLeL798uAMeaDbcnPz9Z7jB2L8lQ0tay-UkCaIW7cfCpUXYtP7EAYZYpKa7nzod9nRyk9lDm0WjWV2WP7VVMaY5Q6YH5Nsduim3zgPnQLusRhommm5BNvtxzhydHgQyGK0XUeZtfxH79-8ug2ywCzp8Cp5xf0TBIyA79fRgh8WMKGQ-cCIUT0gUb4zHZ7GJI7equH7O7i_HZ9WVzffL9af7suUOp6LmSpTKV7QN2plUJXiRaUNgBOCmilbNFIdGXzJ1dYoxFt2_W9yrAGcdXLQ3b2yjstbf4YXZgjDHaKfoS4tQTe_j8J_t5u6MlqmcWSTSb48kYQ6XFxabajT-iGAYKjJdmsvtArUzUqQ8UrFCOlFF3_fkaU9sUl-88l--JS3jn5-N_7xl9P5G9tPZQv</recordid><startdate>20170214</startdate><enddate>20170214</enddate><creator>Joo, Jong Cheon</creator><creator>Hwang, Jung Hoo</creator><creator>Jo, Eunbi</creator><creator>Kim, Young-Rang</creator><creator>Kim, Dae Joon</creator><creator>Lee, Kyung-Bok</creator><creator>Park, Soo Jung</creator><creator>Jang, Ik-Soon</creator><general>Impact Journals LLC</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170214</creationdate><title>Cordycepin induces apoptosis by caveolin-1-mediated JNK regulation of Foxo3a in human lung adenocarcinoma</title><author>Joo, Jong Cheon ; Hwang, Jung Hoo ; Jo, Eunbi ; Kim, Young-Rang ; Kim, Dae Joon ; Lee, Kyung-Bok ; Park, Soo Jung ; Jang, Ik-Soon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-304925fac5d474ce21ba459aae31ab33bc93ce0893ce2c6c91bbdff41ba8cc7f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>A549 Cells</topic><topic>Adenocarcinoma - drug therapy</topic><topic>Adenocarcinoma - genetics</topic><topic>Adenocarcinoma - metabolism</topic><topic>Animals</topic><topic>Anthracenes - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - genetics</topic><topic>Blotting, Western</topic><topic>Caveolin 1 - genetics</topic><topic>Caveolin 1 - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Deoxyadenosines - pharmacology</topic><topic>Forkhead Box Protein O3 - genetics</topic><topic>Forkhead Box Protein O3 - metabolism</topic><topic>Gene Expression Profiling - methods</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Gene Ontology</topic><topic>Gene Regulatory Networks</topic><topic>Humans</topic><topic>JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors</topic><topic>JNK Mitogen-Activated Protein Kinases - genetics</topic><topic>JNK Mitogen-Activated Protein Kinases - metabolism</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Microscopy, Fluorescence</topic><topic>Phosphorylation - drug effects</topic><topic>Research Paper</topic><topic>RNA Interference</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - genetics</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>online_resources</toplevel><creatorcontrib>Joo, Jong Cheon</creatorcontrib><creatorcontrib>Hwang, Jung Hoo</creatorcontrib><creatorcontrib>Jo, Eunbi</creatorcontrib><creatorcontrib>Kim, Young-Rang</creatorcontrib><creatorcontrib>Kim, Dae Joon</creatorcontrib><creatorcontrib>Lee, Kyung-Bok</creatorcontrib><creatorcontrib>Park, Soo Jung</creatorcontrib><creatorcontrib>Jang, Ik-Soon</creatorcontrib><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Joo, Jong Cheon</au><au>Hwang, Jung Hoo</au><au>Jo, Eunbi</au><au>Kim, Young-Rang</au><au>Kim, Dae Joon</au><au>Lee, Kyung-Bok</au><au>Park, Soo Jung</au><au>Jang, Ik-Soon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cordycepin induces apoptosis by caveolin-1-mediated JNK regulation of Foxo3a in human lung adenocarcinoma</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2017-02-14</date><risdate>2017</risdate><volume>8</volume><issue>7</issue><spage>12211</spage><epage>12224</epage><pages>12211-12224</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>Forkhead transcription factor (Foxo3a) is a downstream effector of JNK-induced tumor suppression. However, it is not clear whether the caveolin-1 (CAV1)-mediated JNK/Foxo3a pathway is involved in cancer cell apoptosis. We found that cordycepin upregulates CAV1 expression, which was accompanied by JNK phosphorylation (p-JNK) and subsequent Foxo3a translocation into the nucleus, resulting in the upregulation of Bax protein expression. Furthermore, we found that CAV1 overexpression upregulated p-JNK, whereas CAV1 siRNA downregulated p-JNK. Additionally, SP600125, a specific JNK inhibitor, significantly increased Foxo3a phosphorylation, which downregulated Foxo3a translocation into the nucleus, indicating that CAV1 mediates JNK regulation of Foxo3a. Foxo3a siRNA downregulated Bax protein and attenuated A549 apoptosis, indicating that the CAV1-mediated JNK/Foxo3a pathway induces the apoptosis of A549 lung cancer cells. Cordycepin significantly decreased tumor volume in nude mice. Taken together, these results indicate that cordycepin promotes CAV1 upregulation to enhance JNK/Foxo3a signaling pathway activation, inducing apoptosis in lung cancer cells, and support its potential as a therapeutic agent for lung cancer.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>28099944</pmid><doi>10.18632/oncotarget.14661</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | A549 Cells Adenocarcinoma - drug therapy Adenocarcinoma - genetics Adenocarcinoma - metabolism Animals Anthracenes - pharmacology Apoptosis - drug effects Apoptosis - genetics Blotting, Western Caveolin 1 - genetics Caveolin 1 - metabolism Cell Line, Tumor Deoxyadenosines - pharmacology Forkhead Box Protein O3 - genetics Forkhead Box Protein O3 - metabolism Gene Expression Profiling - methods Gene Expression Regulation, Neoplastic - drug effects Gene Ontology Gene Regulatory Networks Humans JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors JNK Mitogen-Activated Protein Kinases - genetics JNK Mitogen-Activated Protein Kinases - metabolism Lung Neoplasms - drug therapy Lung Neoplasms - genetics Lung Neoplasms - metabolism Mice, Inbred BALB C Mice, Nude Microscopy, Fluorescence Phosphorylation - drug effects Research Paper RNA Interference Signal Transduction - drug effects Signal Transduction - genetics Xenograft Model Antitumor Assays |
| title | Cordycepin induces apoptosis by caveolin-1-mediated JNK regulation of Foxo3a in human lung adenocarcinoma |
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