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<title xml:lang="en">Cordycepin inhibits human ovarian cancer by inducing autophagy and apoptosis through Dickkopf-related protein 1/β-catenin signaling</title>
<author>
<name sortKey="Jang, Hyun Jin" sort="Jang, Hyun Jin" uniqKey="Jang H" first="Hyun-Jin" last="Jang">Hyun-Jin Jang</name>
<affiliation>
<nlm:aff id="au1">
<institution>Division of Bioconvergence Analysis, Korea Basic Science Institute</institution>
<addr-line>Daejeon 305-333, Republic of Korea</addr-line>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="au2">
<institution>Department of Biological Sciences, Sungkyunkwan University</institution>
<addr-line>Suwon 16419, Republic of Korea</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Yang, Kyeong Eun" sort="Yang, Kyeong Eun" uniqKey="Yang K" first="Kyeong Eun" last="Yang">Kyeong Eun Yang</name>
<affiliation>
<nlm:aff id="au1">
<institution>Division of Bioconvergence Analysis, Korea Basic Science Institute</institution>
<addr-line>Daejeon 305-333, Republic of Korea</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Hwang, In Hu" sort="Hwang, In Hu" uniqKey="Hwang I" first="In-Hu" last="Hwang">In-Hu Hwang</name>
<affiliation>
<nlm:aff id="au3">
<institution>Neuroscience Research Institute, Korea University College of Medicine</institution>
<addr-line>Seoul 136-705, Republic of Korea</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Huh, Yang Hoon" sort="Huh, Yang Hoon" uniqKey="Huh Y" first="Yang Hoon" last="Huh">Yang Hoon Huh</name>
<affiliation>
<nlm:aff id="au4">
<institution>Electron Microscopy Research Center, Korea Basic Science Institute</institution>
<addr-line>Cheongju 28119, Republic of Korea</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Kim, Dae Joon" sort="Kim, Dae Joon" uniqKey="Kim D" first="Dae Joon" last="Kim">Dae Joon Kim</name>
<affiliation>
<nlm:aff id="au5">
<institution>Department of Biomedical Sciences, School of Medicine, University of Texas Rio Grande Valley</institution>
<addr-line>Edinburg, Texas, USA</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Yoo, Hwa Seung" sort="Yoo, Hwa Seung" uniqKey="Yoo H" first="Hwa-Seung" last="Yoo">Hwa-Seung Yoo</name>
<affiliation>
<nlm:aff id="au6">
<institution>East-West Cancer Center, Daejeon University</institution>
<addr-line>Daejeon 302-120, Korea</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Park, Soo Jung" sort="Park, Soo Jung" uniqKey="Park S" first="Soo Jung" last="Park">Soo Jung Park</name>
<affiliation>
<nlm:aff id="au7">
<institution>Department of Sasang Constitutional Medicine, College of Korean Medicine, Woosuk University</institution>
<addr-line>Wanju, Jeonbuk 55338, Republic of Korea</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Jang, Ik Soon" sort="Jang, Ik Soon" uniqKey="Jang I" first="Ik-Soon" last="Jang">Ik-Soon Jang</name>
<affiliation>
<nlm:aff id="au1">
<institution>Division of Bioconvergence Analysis, Korea Basic Science Institute</institution>
<addr-line>Daejeon 305-333, Republic of Korea</addr-line>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="au8">
<institution>Division of Analytical Science, University of Science and Technology</institution>
<addr-line>Daejeon 34113, Republic of Korea</addr-line>
</nlm:aff>
</affiliation>
</author>
</titleStmt>
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<idno type="wicri:source">PMC</idno>
<idno type="pmid">31814895</idno>
<idno type="pmc">6895532</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895532</idno>
<idno type="RBID">PMC:6895532</idno>
<date when="2019">2019</date>
<idno type="wicri:Area/Pmc/Corpus">000357</idno>
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<analytic>
<title xml:lang="en" level="a" type="main">Cordycepin inhibits human ovarian cancer by inducing autophagy and apoptosis through Dickkopf-related protein 1/β-catenin signaling</title>
<author>
<name sortKey="Jang, Hyun Jin" sort="Jang, Hyun Jin" uniqKey="Jang H" first="Hyun-Jin" last="Jang">Hyun-Jin Jang</name>
<affiliation>
<nlm:aff id="au1">
<institution>Division of Bioconvergence Analysis, Korea Basic Science Institute</institution>
<addr-line>Daejeon 305-333, Republic of Korea</addr-line>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="au2">
<institution>Department of Biological Sciences, Sungkyunkwan University</institution>
<addr-line>Suwon 16419, Republic of Korea</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Yang, Kyeong Eun" sort="Yang, Kyeong Eun" uniqKey="Yang K" first="Kyeong Eun" last="Yang">Kyeong Eun Yang</name>
<affiliation>
<nlm:aff id="au1">
<institution>Division of Bioconvergence Analysis, Korea Basic Science Institute</institution>
<addr-line>Daejeon 305-333, Republic of Korea</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Hwang, In Hu" sort="Hwang, In Hu" uniqKey="Hwang I" first="In-Hu" last="Hwang">In-Hu Hwang</name>
<affiliation>
<nlm:aff id="au3">
<institution>Neuroscience Research Institute, Korea University College of Medicine</institution>
<addr-line>Seoul 136-705, Republic of Korea</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Huh, Yang Hoon" sort="Huh, Yang Hoon" uniqKey="Huh Y" first="Yang Hoon" last="Huh">Yang Hoon Huh</name>
<affiliation>
<nlm:aff id="au4">
<institution>Electron Microscopy Research Center, Korea Basic Science Institute</institution>
<addr-line>Cheongju 28119, Republic of Korea</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Kim, Dae Joon" sort="Kim, Dae Joon" uniqKey="Kim D" first="Dae Joon" last="Kim">Dae Joon Kim</name>
<affiliation>
<nlm:aff id="au5">
<institution>Department of Biomedical Sciences, School of Medicine, University of Texas Rio Grande Valley</institution>
<addr-line>Edinburg, Texas, USA</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Yoo, Hwa Seung" sort="Yoo, Hwa Seung" uniqKey="Yoo H" first="Hwa-Seung" last="Yoo">Hwa-Seung Yoo</name>
<affiliation>
<nlm:aff id="au6">
<institution>East-West Cancer Center, Daejeon University</institution>
<addr-line>Daejeon 302-120, Korea</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Park, Soo Jung" sort="Park, Soo Jung" uniqKey="Park S" first="Soo Jung" last="Park">Soo Jung Park</name>
<affiliation>
<nlm:aff id="au7">
<institution>Department of Sasang Constitutional Medicine, College of Korean Medicine, Woosuk University</institution>
<addr-line>Wanju, Jeonbuk 55338, Republic of Korea</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Jang, Ik Soon" sort="Jang, Ik Soon" uniqKey="Jang I" first="Ik-Soon" last="Jang">Ik-Soon Jang</name>
<affiliation>
<nlm:aff id="au1">
<institution>Division of Bioconvergence Analysis, Korea Basic Science Institute</institution>
<addr-line>Daejeon 305-333, Republic of Korea</addr-line>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="au8">
<institution>Division of Analytical Science, University of Science and Technology</institution>
<addr-line>Daejeon 34113, Republic of Korea</addr-line>
</nlm:aff>
</affiliation>
</author>
</analytic>
<series>
<title level="j">American Journal of Translational Research</title>
<idno type="eISSN">1943-8141</idno>
<imprint>
<date when="2019">2019</date>
</imprint>
</series>
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<front>
<div type="abstract" xml:lang="en">
<p>Cordycepin, the major active component from
<italic>Cordyceps militaris</italic>
, has been reported to significantly inhibit some types of cancer; however, its effects on ovarian cancer are still not well understood. In this study, we treated human ovarian cancer cells with different doses of cordycepin and found that it dose-dependently reduced ovarian cancer cell viability, based on Cell counting kit-8 reagent. Immunoblotting showed that cordycepin increased Dickkopf-related protein 1 (Dkk1) levels and inhibited β-catenin signaling. Atg7 knockdown in ovarian cancer cells significantly inhibited cordycepin-induced apoptosis, whereas β-catenin overexpression abolished the effects of cordycepin on cell death and proliferation. Furthermore, we found that Dkk1 overexpression by transfection downregulated the expression of c-Myc and cyclin D1. siRNA-mediated Dkk1 silencing downregulated the expression of Atg8, beclin, and LC3 and promoted β-catenin translocation from the cytoplasm into the nucleus. These results suggest that cordycepin inhibits ovarian cancer cell growth, possibly through coordinated autophagy and Dkk1/β-catenin signaling. Taken together, our findings provide new insights into the treatment of ovarian cancer using cordycepin.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article">
<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Am J Transl Res</journal-id>
<journal-id journal-id-type="iso-abbrev">Am J Transl Res</journal-id>
<journal-id journal-id-type="publisher-id">ajtr</journal-id>
<journal-title-group>
<journal-title>American Journal of Translational Research</journal-title>
</journal-title-group>
<issn pub-type="epub">1943-8141</issn>
<publisher>
<publisher-name>e-Century Publishing Corporation</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">31814895</article-id>
<article-id pub-id-type="pmc">6895532</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Original Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Cordycepin inhibits human ovarian cancer by inducing autophagy and apoptosis through Dickkopf-related protein 1/β-catenin signaling</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Jang</surname>
<given-names>Hyun-Jin</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
<xref ref-type="aff" rid="au2">2</xref>
<xref ref-type="author-notes" rid="fn1">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Yang</surname>
<given-names>Kyeong Eun</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
<xref ref-type="author-notes" rid="fn1">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hwang</surname>
<given-names>In-Hu</given-names>
</name>
<xref ref-type="aff" rid="au3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Huh</surname>
<given-names>Yang Hoon</given-names>
</name>
<xref ref-type="aff" rid="au4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kim</surname>
<given-names>Dae Joon</given-names>
</name>
<xref ref-type="aff" rid="au5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Yoo</surname>
<given-names>Hwa-Seung</given-names>
</name>
<xref ref-type="aff" rid="au6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Park</surname>
<given-names>Soo Jung</given-names>
</name>
<xref ref-type="aff" rid="au7">7</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Jang</surname>
<given-names>Ik-Soon</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
<xref ref-type="aff" rid="au8">8</xref>
</contrib>
<aff id="au1">
<label>1</label>
<institution>Division of Bioconvergence Analysis, Korea Basic Science Institute</institution>
<addr-line>Daejeon 305-333, Republic of Korea</addr-line>
</aff>
<aff id="au2">
<label>2</label>
<institution>Department of Biological Sciences, Sungkyunkwan University</institution>
<addr-line>Suwon 16419, Republic of Korea</addr-line>
</aff>
<aff id="au3">
<label>3</label>
<institution>Neuroscience Research Institute, Korea University College of Medicine</institution>
<addr-line>Seoul 136-705, Republic of Korea</addr-line>
</aff>
<aff id="au4">
<label>4</label>
<institution>Electron Microscopy Research Center, Korea Basic Science Institute</institution>
<addr-line>Cheongju 28119, Republic of Korea</addr-line>
</aff>
<aff id="au5">
<label>5</label>
<institution>Department of Biomedical Sciences, School of Medicine, University of Texas Rio Grande Valley</institution>
<addr-line>Edinburg, Texas, USA</addr-line>
</aff>
<aff id="au6">
<label>6</label>
<institution>East-West Cancer Center, Daejeon University</institution>
<addr-line>Daejeon 302-120, Korea</addr-line>
</aff>
<aff id="au7">
<label>7</label>
<institution>Department of Sasang Constitutional Medicine, College of Korean Medicine, Woosuk University</institution>
<addr-line>Wanju, Jeonbuk 55338, Republic of Korea</addr-line>
</aff>
<aff id="au8">
<label>8</label>
<institution>Division of Analytical Science, University of Science and Technology</institution>
<addr-line>Daejeon 34113, Republic of Korea</addr-line>
</aff>
</contrib-group>
<author-notes>
<corresp>
<bold>Address correspondence to:</bold>
Dr. Ik-Soon Jang, Division of Bioconvergence Analysis, Korea Basic Science Institute, Gwahangno 113, Yuseong-gu, Daejeon 305-333, Republic of Korea. Tel: +82-865-3430; Fax: +82-865-3419; E-mail:
<email>jangiksn@kbsi.re.kr</email>
; Soo Jung Park, Department of Sasang Constitutional Medicine, College of Korean Medicine, Woosuk University, Wanju, Jeonbuk 55338, Republic of Korea. Tel: +82-010-6287-0248; E-mail:
<email>taorgi@daum.net</email>
</corresp>
<fn id="fn1">
<label>*</label>
<p>Equal contributors.</p>
</fn>
</author-notes>
<pub-date pub-type="collection">
<year>2019</year>
</pub-date>
<pub-date pub-type="epub">
<day>15</day>
<month>11</month>
<year>2019</year>
</pub-date>
<volume>11</volume>
<issue>11</issue>
<fpage>6890</fpage>
<lpage>6906</lpage>
<history>
<date date-type="received">
<day>27</day>
<month>5</month>
<year>2019</year>
</date>
<date date-type="accepted">
<day>31</day>
<month>7</month>
<year>2019</year>
</date>
</history>
<permissions>
<copyright-statement>AJTR Copyright © 2019</copyright-statement>
<copyright-year>2019</copyright-year>
</permissions>
<abstract>
<p>Cordycepin, the major active component from
<italic>Cordyceps militaris</italic>
, has been reported to significantly inhibit some types of cancer; however, its effects on ovarian cancer are still not well understood. In this study, we treated human ovarian cancer cells with different doses of cordycepin and found that it dose-dependently reduced ovarian cancer cell viability, based on Cell counting kit-8 reagent. Immunoblotting showed that cordycepin increased Dickkopf-related protein 1 (Dkk1) levels and inhibited β-catenin signaling. Atg7 knockdown in ovarian cancer cells significantly inhibited cordycepin-induced apoptosis, whereas β-catenin overexpression abolished the effects of cordycepin on cell death and proliferation. Furthermore, we found that Dkk1 overexpression by transfection downregulated the expression of c-Myc and cyclin D1. siRNA-mediated Dkk1 silencing downregulated the expression of Atg8, beclin, and LC3 and promoted β-catenin translocation from the cytoplasm into the nucleus. These results suggest that cordycepin inhibits ovarian cancer cell growth, possibly through coordinated autophagy and Dkk1/β-catenin signaling. Taken together, our findings provide new insights into the treatment of ovarian cancer using cordycepin.</p>
</abstract>
<kwd-group>
<kwd>Apoptosis</kwd>
<kwd>Dickkopf-related protein 1</kwd>
<kwd>β-catenin</kwd>
<kwd>autophagy</kwd>
<kwd>cordycepin</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>

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