Survivin Promotes Piperlongumine Resistance in Ovarian Cancer
Identifieur interne : 000374 ( Pmc/Checkpoint ); précédent : 000373; suivant : 000375Survivin Promotes Piperlongumine Resistance in Ovarian Cancer
Auteurs : Xing-Wei Nan [République populaire de Chine] ; Li-Hua Gong [République populaire de Chine] ; Xu Chen [République populaire de Chine] ; Hai-Hong Zhou [République populaire de Chine] ; Piao-Piao Ye [République populaire de Chine] ; Yang Yang [République populaire de Chine] ; Zi-Hao Xing [République populaire de Chine] ; Meng-Ning Wei [République populaire de Chine] ; Yao Li [République populaire de Chine] ; Sheng-Te Wang [République populaire de Chine] ; Kun Liu [République populaire de Chine] ; Zhi Shi [République populaire de Chine] ; Xiao-Jian Yan [République populaire de Chine]Source :
- Frontiers in Oncology [ 2234-943X ] ; 2019.
Abstract
Ovarian cancer is one of the most fatal female malignancies while targeting apoptosis is critical for improving ovarian cancer patients' lives. Survivin is regarded as the most robust anti-apoptosis protein, and its overexpression in ovarian cancer is related to poor survival and apoptosis resistance. Piperlongumine (PL) extracted from peppers is defined as an active alkaloid/amide and exhibits a broad spectrum of antitumor effects. Here, we demonstrate that PL induces the rapid depletion of survivin protein levels via reactive oxygen species (ROS)-mediated proteasome-dependent pathway
Url:
DOI: 10.3389/fonc.2019.01345
PubMed: 31850227
PubMed Central: 6895030
Affiliations:
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<author><name sortKey="Yan, Xiao Jian" sort="Yan, Xiao Jian" uniqKey="Yan X" first="Xiao-Jian" last="Yan">Xiao-Jian Yan</name>
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<series><title level="j">Frontiers in Oncology</title>
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<front><div type="abstract" xml:lang="en"><p>Ovarian cancer is one of the most fatal female malignancies while targeting apoptosis is critical for improving ovarian cancer patients' lives. Survivin is regarded as the most robust anti-apoptosis protein, and its overexpression in ovarian cancer is related to poor survival and apoptosis resistance. Piperlongumine (PL) extracted from peppers is defined as an active alkaloid/amide and exhibits a broad spectrum of antitumor effects. Here, we demonstrate that PL induces the rapid depletion of survivin protein levels via reactive oxygen species (ROS)-mediated proteasome-dependent pathway <italic>in vitro</italic>
, while exerting a remarkable inhibitory influence on the proliferation of ovarian cancer cells. Overexpression of survivin raises the survival rate of ovarian cancer cells to PL. Moreover, PL inhibits ovarian cancer cells xenograft tumor growth and downregulates survivin <italic>in vivo</italic>
. Our findings reveal a previously unrecognized mechanism of PL in suppressing survivin expression as well as survivin promotes piperlongumine resistance in ovarian cancer and suggest that ROS-mediated proteasome-dependent pathway can be exploited to overcome apoptosis resistance triggered by aberrant expression of survivin.</p>
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<journal-id journal-id-type="iso-abbrev">Front Oncol</journal-id>
<journal-id journal-id-type="publisher-id">Front. Oncol.</journal-id>
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<issn pub-type="epub">2234-943X</issn>
<publisher><publisher-name>Frontiers Media S.A.</publisher-name>
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<article-meta><article-id pub-id-type="pmid">31850227</article-id>
<article-id pub-id-type="pmc">6895030</article-id>
<article-id pub-id-type="doi">10.3389/fonc.2019.01345</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Oncology</subject>
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<title-group><article-title>Survivin Promotes Piperlongumine Resistance in Ovarian Cancer</article-title>
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<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
<uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/655818/overview"></uri>
</contrib>
<contrib contrib-type="author"><name><surname>Li</surname>
<given-names>Yao</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wang</surname>
<given-names>Sheng-Te</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Liu</surname>
<given-names>Kun</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Shi</surname>
<given-names>Zhi</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
<xref ref-type="corresp" rid="c001"><sup>*</sup>
</xref>
<uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/542636/overview"></uri>
</contrib>
<contrib contrib-type="author"><name><surname>Yan</surname>
<given-names>Xiao-Jian</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
<xref ref-type="corresp" rid="c002"><sup>*</sup>
</xref>
<uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/667641/overview"></uri>
</contrib>
</contrib-group>
<aff id="aff1"><sup>1</sup>
<institution>Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University</institution>
,<addr-line>Wenzhou</addr-line>
,<country>China</country>
</aff>
<aff id="aff2"><sup>2</sup>
<institution>Guangdong Provincial Key Laboratory of Bioengineering Medicine, Department of Cell Biology and Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University</institution>
,<addr-line>Guangzhou</addr-line>
,<country>China</country>
</aff>
<aff id="aff3"><sup>3</sup>
<institution>Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Women's Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine</institution>
,<addr-line>Hangzhou</addr-line>
,<country>China</country>
</aff>
<author-notes><fn fn-type="edited-by"><p>Edited by: Chang Zou, Shenzhen People's Hospital, China</p>
</fn>
<fn fn-type="edited-by"><p>Reviewed by: Qing Wang, Sun Yat-sen University, China; Shuangping Liu, Dalian University, China</p>
</fn>
<corresp id="c001">*Correspondence: Zhi Shi <email>tshizhi@jnu.edu.cn</email>
</corresp>
<corresp id="c002">Xiao-Jian Yan <email>yxjbetter@126.com</email>
</corresp>
<fn fn-type="other" id="fn001"><p>This article was submitted to Molecular and Cellular Oncology, a section of the journal Frontiers in Oncology</p>
</fn>
<fn fn-type="other" id="fn002"><p>†These authors have contributed equally to this work</p>
</fn>
</author-notes>
<pub-date pub-type="epub"><day>29</day>
<month>11</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="collection"><year>2019</year>
</pub-date>
<volume>9</volume>
<elocation-id>1345</elocation-id>
<history><date date-type="received"><day>27</day>
<month>9</month>
<year>2019</year>
</date>
<date date-type="accepted"><day>15</day>
<month>11</month>
<year>2019</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2019 Nan, Gong, Chen, Zhou, Ye, Yang, Xing, Wei, Li, Wang, Liu, Shi and Yan.</copyright-statement>
<copyright-year>2019</copyright-year>
<copyright-holder>Nan, Gong, Chen, Zhou, Ye, Yang, Xing, Wei, Li, Wang, Liu, Shi and Yan</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p>
</license>
</permissions>
<abstract><p>Ovarian cancer is one of the most fatal female malignancies while targeting apoptosis is critical for improving ovarian cancer patients' lives. Survivin is regarded as the most robust anti-apoptosis protein, and its overexpression in ovarian cancer is related to poor survival and apoptosis resistance. Piperlongumine (PL) extracted from peppers is defined as an active alkaloid/amide and exhibits a broad spectrum of antitumor effects. Here, we demonstrate that PL induces the rapid depletion of survivin protein levels via reactive oxygen species (ROS)-mediated proteasome-dependent pathway <italic>in vitro</italic>
, while exerting a remarkable inhibitory influence on the proliferation of ovarian cancer cells. Overexpression of survivin raises the survival rate of ovarian cancer cells to PL. Moreover, PL inhibits ovarian cancer cells xenograft tumor growth and downregulates survivin <italic>in vivo</italic>
. Our findings reveal a previously unrecognized mechanism of PL in suppressing survivin expression as well as survivin promotes piperlongumine resistance in ovarian cancer and suggest that ROS-mediated proteasome-dependent pathway can be exploited to overcome apoptosis resistance triggered by aberrant expression of survivin.</p>
</abstract>
<kwd-group><kwd>piperlongumine</kwd>
<kwd>survivin</kwd>
<kwd>ovarian cancer</kwd>
<kwd>ROS</kwd>
<kwd>proteasome</kwd>
</kwd-group>
<counts><fig-count count="6"></fig-count>
<table-count count="0"></table-count>
<equation-count count="0"></equation-count>
<ref-count count="45"></ref-count>
<page-count count="11"></page-count>
<word-count count="5439"></word-count>
</counts>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>République populaire de Chine</li>
</country>
</list>
<tree><country name="République populaire de Chine"><noRegion><name sortKey="Nan, Xing Wei" sort="Nan, Xing Wei" uniqKey="Nan X" first="Xing-Wei" last="Nan">Xing-Wei Nan</name>
</noRegion>
<name sortKey="Chen, Xu" sort="Chen, Xu" uniqKey="Chen X" first="Xu" last="Chen">Xu Chen</name>
<name sortKey="Gong, Li Hua" sort="Gong, Li Hua" uniqKey="Gong L" first="Li-Hua" last="Gong">Li-Hua Gong</name>
<name sortKey="Li, Yao" sort="Li, Yao" uniqKey="Li Y" first="Yao" last="Li">Yao Li</name>
<name sortKey="Liu, Kun" sort="Liu, Kun" uniqKey="Liu K" first="Kun" last="Liu">Kun Liu</name>
<name sortKey="Shi, Zhi" sort="Shi, Zhi" uniqKey="Shi Z" first="Zhi" last="Shi">Zhi Shi</name>
<name sortKey="Wang, Sheng Te" sort="Wang, Sheng Te" uniqKey="Wang S" first="Sheng-Te" last="Wang">Sheng-Te Wang</name>
<name sortKey="Wei, Meng Ning" sort="Wei, Meng Ning" uniqKey="Wei M" first="Meng-Ning" last="Wei">Meng-Ning Wei</name>
<name sortKey="Xing, Zi Hao" sort="Xing, Zi Hao" uniqKey="Xing Z" first="Zi-Hao" last="Xing">Zi-Hao Xing</name>
<name sortKey="Yan, Xiao Jian" sort="Yan, Xiao Jian" uniqKey="Yan X" first="Xiao-Jian" last="Yan">Xiao-Jian Yan</name>
<name sortKey="Yan, Xiao Jian" sort="Yan, Xiao Jian" uniqKey="Yan X" first="Xiao-Jian" last="Yan">Xiao-Jian Yan</name>
<name sortKey="Yang, Yang" sort="Yang, Yang" uniqKey="Yang Y" first="Yang" last="Yang">Yang Yang</name>
<name sortKey="Ye, Piao Piao" sort="Ye, Piao Piao" uniqKey="Ye P" first="Piao-Piao" last="Ye">Piao-Piao Ye</name>
<name sortKey="Zhou, Hai Hong" sort="Zhou, Hai Hong" uniqKey="Zhou H" first="Hai-Hong" last="Zhou">Hai-Hong Zhou</name>
</country>
</tree>
</affiliations>
</record>
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