Pristimerin induces apoptosis and autophagy via activation of ROS/ASK1/JNK pathway in human breast cancer in vitro and in vivo
Breast cancer is the most common malignant tumor in women, and progress toward long-term survival has stagnated. Pristimerin, a natural quinonemethide triterpenoid, exhibits potential anti-tumor effects on various cancers. However, the underlying mechanism remains poorly understood. In this study, w...
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| Veröffentlicht in: | Cell death discovery 2019-08, Vol.5 (1), p.125-13, Article 125 |
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| creator | Zhao, Qun Liu, Yingxiang Zhong, Jing Bi, Yun Liu, Yongqiang Ren, Ziting Li, Xiang Jia, Junjun Yu, Mengting Yu, Xianjun |
| description | Breast cancer is the most common malignant tumor in women, and progress toward long-term survival has stagnated. Pristimerin, a natural quinonemethide triterpenoid, exhibits potential anti-tumor effects on various cancers. However, the underlying mechanism remains poorly understood. In this study, we found that pristimerin reduced the viability of breast cancer cells in vitro and the growth of xenografts in vivo, and these reductions were accompanied by thioredoxin-1 (Trx-1) inhibition and ASK1 and JNK activation. The results showed that pristimerin inhibited cell cycle progression and triggered cell apoptosis and autophagy. Furthermore, we found that the generation of reactive oxygen species (ROS) was a critical mediator in pristimerin-induced cell death. Enhanced ROS generation by pristimerin activated the ASK1/JNK signaling pathway. Inhibition of ROS with N-acetyl cysteine (NAC) significantly decreased pristimerin-induced cell death by inhibiting the phosphorylation of ASK1 and JNK. Taken together, these results suggest a critical role for the ROS/ASK1/JNK pathway in the anticancer activity of pristimerin. |
| doi_str_mv | 10.1038/s41420-019-0208-0 |
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Pristimerin, a natural quinonemethide triterpenoid, exhibits potential anti-tumor effects on various cancers. However, the underlying mechanism remains poorly understood. In this study, we found that pristimerin reduced the viability of breast cancer cells in vitro and the growth of xenografts in vivo, and these reductions were accompanied by thioredoxin-1 (Trx-1) inhibition and ASK1 and JNK activation. The results showed that pristimerin inhibited cell cycle progression and triggered cell apoptosis and autophagy. Furthermore, we found that the generation of reactive oxygen species (ROS) was a critical mediator in pristimerin-induced cell death. Enhanced ROS generation by pristimerin activated the ASK1/JNK signaling pathway. Inhibition of ROS with N-acetyl cysteine (NAC) significantly decreased pristimerin-induced cell death by inhibiting the phosphorylation of ASK1 and JNK. Taken together, these results suggest a critical role for the ROS/ASK1/JNK pathway in the anticancer activity of pristimerin.</description><identifier>ISSN: 2058-7716</identifier><identifier>EISSN: 2058-7716</identifier><identifier>DOI: 10.1038/s41420-019-0208-0</identifier><identifier>PMID: 31396402</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/154/436 ; 631/67/1347 ; Acetylcysteine ; Antitumor activity ; Apoptosis ; Autophagy ; Biochemistry ; Biomedical and Life Sciences ; Breast cancer ; Cell Biology ; Cell cycle ; Cell Cycle Analysis ; Cell death ; Life Sciences ; MAP kinase ; Phagocytosis ; Phosphorylation ; Reactive oxygen species ; Signal transduction ; Stem Cells ; Thioredoxin ; Xenografts</subject><ispartof>Cell death discovery, 2019-08, Vol.5 (1), p.125-13, Article 125</ispartof><rights>The Author(s) 2019</rights><rights>2019. This work is published under http://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><citedby>FETCH-LOGICAL-c536t-53169fcb0fcfc9e8b1ea3f4f66493a880c403859f415ac8286e808c21e91f86a3</citedby><cites>FETCH-LOGICAL-c536t-53169fcb0fcfc9e8b1ea3f4f66493a880c403859f415ac8286e808c21e91f86a3</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/PMC6680048/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680048/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27922,27923,41118,42187,51574,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31396402$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhao, Qun</creatorcontrib><creatorcontrib>Liu, Yingxiang</creatorcontrib><creatorcontrib>Zhong, Jing</creatorcontrib><creatorcontrib>Bi, Yun</creatorcontrib><creatorcontrib>Liu, Yongqiang</creatorcontrib><creatorcontrib>Ren, Ziting</creatorcontrib><creatorcontrib>Li, Xiang</creatorcontrib><creatorcontrib>Jia, Junjun</creatorcontrib><creatorcontrib>Yu, Mengting</creatorcontrib><creatorcontrib>Yu, Xianjun</creatorcontrib><title>Pristimerin induces apoptosis and autophagy via activation of ROS/ASK1/JNK pathway in human breast cancer in vitro and in vivo</title><title>Cell death discovery</title><addtitle>Cell Death Discov</addtitle><addtitle>Cell Death Discov</addtitle><description>Breast cancer is the most common malignant tumor in women, and progress toward long-term survival has stagnated. Pristimerin, a natural quinonemethide triterpenoid, exhibits potential anti-tumor effects on various cancers. However, the underlying mechanism remains poorly understood. In this study, we found that pristimerin reduced the viability of breast cancer cells in vitro and the growth of xenografts in vivo, and these reductions were accompanied by thioredoxin-1 (Trx-1) inhibition and ASK1 and JNK activation. The results showed that pristimerin inhibited cell cycle progression and triggered cell apoptosis and autophagy. Furthermore, we found that the generation of reactive oxygen species (ROS) was a critical mediator in pristimerin-induced cell death. Enhanced ROS generation by pristimerin activated the ASK1/JNK signaling pathway. Inhibition of ROS with N-acetyl cysteine (NAC) significantly decreased pristimerin-induced cell death by inhibiting the phosphorylation of ASK1 and JNK. Taken together, these results suggest a critical role for the ROS/ASK1/JNK pathway in the anticancer activity of pristimerin.</description><subject>631/154/436</subject><subject>631/67/1347</subject><subject>Acetylcysteine</subject><subject>Antitumor activity</subject><subject>Apoptosis</subject><subject>Autophagy</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Breast cancer</subject><subject>Cell Biology</subject><subject>Cell cycle</subject><subject>Cell Cycle Analysis</subject><subject>Cell death</subject><subject>Life Sciences</subject><subject>MAP kinase</subject><subject>Phagocytosis</subject><subject>Phosphorylation</subject><subject>Reactive oxygen species</subject><subject>Signal transduction</subject><subject>Stem Cells</subject><subject>Thioredoxin</subject><subject>Xenografts</subject><issn>2058-7716</issn><issn>2058-7716</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kcFu1DAQhiMEolXpA3BBlrhwSXfsJI5zQaqqQqEVRRTO1qzX3nW1sYPtBO2FZ8fpllKQOHns-eYfz_xF8ZLCCYVKLGJNawYl0K4EBqKEJ8Uhg0aUbUv500fxQXEc4y0A0KatW1E9Lw4qWnW8BnZY_PwcbEy218E6Yt1qVDoSHPyQfLQ5ciuCY_LDBtc7MlkkqJKdMFnviDfky_XN4vTmki4-frokA6bND9xlGbIZe3RkGTTGRBQ6pcP8PNkU_J3o3WXyL4pnBrdRH9-fR8W3d-dfzy7Kq-v3H85Or0rVVDyVTUV5Z9QSjDKq02JJNVamNpzXXYVCgKrzSprO1LRBJZjgWoBQjOqOGsGxOire7nWHcdnrldIuBdzKIdgew056tPLvjLMbufaT5FwA1CILvLkXCP77qGOSvY1Kb7fotB-jZKzNCwbWNRl9_Q9668fg8niZ4mJG2EzRPaWCjzFo8_AZCnI2WO4NltlgORssIde8ejzFQ8VvOzPA9kDMKbfW4U_r_6v-As-usWU</recordid><startdate>20190805</startdate><enddate>20190805</enddate><creator>Zhao, Qun</creator><creator>Liu, Yingxiang</creator><creator>Zhong, Jing</creator><creator>Bi, Yun</creator><creator>Liu, Yongqiang</creator><creator>Ren, Ziting</creator><creator>Li, Xiang</creator><creator>Jia, Junjun</creator><creator>Yu, Mengting</creator><creator>Yu, Xianjun</creator><general>Nature Publishing Group UK</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</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>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20190805</creationdate><title>Pristimerin induces apoptosis and autophagy via activation of ROS/ASK1/JNK pathway in human breast cancer in vitro and in vivo</title><author>Zhao, Qun ; Liu, Yingxiang ; Zhong, Jing ; Bi, Yun ; Liu, Yongqiang ; Ren, Ziting ; Li, Xiang ; Jia, Junjun ; Yu, Mengting ; Yu, Xianjun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c536t-53169fcb0fcfc9e8b1ea3f4f66493a880c403859f415ac8286e808c21e91f86a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>631/154/436</topic><topic>631/67/1347</topic><topic>Acetylcysteine</topic><topic>Antitumor activity</topic><topic>Apoptosis</topic><topic>Autophagy</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Breast cancer</topic><topic>Cell Biology</topic><topic>Cell cycle</topic><topic>Cell Cycle Analysis</topic><topic>Cell death</topic><topic>Life Sciences</topic><topic>MAP kinase</topic><topic>Phagocytosis</topic><topic>Phosphorylation</topic><topic>Reactive oxygen species</topic><topic>Signal transduction</topic><topic>Stem Cells</topic><topic>Thioredoxin</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhao, Qun</creatorcontrib><creatorcontrib>Liu, Yingxiang</creatorcontrib><creatorcontrib>Zhong, Jing</creatorcontrib><creatorcontrib>Bi, Yun</creatorcontrib><creatorcontrib>Liu, Yongqiang</creatorcontrib><creatorcontrib>Ren, Ziting</creatorcontrib><creatorcontrib>Li, Xiang</creatorcontrib><creatorcontrib>Jia, Junjun</creatorcontrib><creatorcontrib>Yu, Mengting</creatorcontrib><creatorcontrib>Yu, Xianjun</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</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</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</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>Biological Science 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 China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell death discovery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhao, Qun</au><au>Liu, Yingxiang</au><au>Zhong, Jing</au><au>Bi, Yun</au><au>Liu, Yongqiang</au><au>Ren, Ziting</au><au>Li, Xiang</au><au>Jia, Junjun</au><au>Yu, Mengting</au><au>Yu, Xianjun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pristimerin induces apoptosis and autophagy via activation of ROS/ASK1/JNK pathway in human breast cancer in vitro and in vivo</atitle><jtitle>Cell death discovery</jtitle><stitle>Cell Death Discov</stitle><addtitle>Cell Death Discov</addtitle><date>2019-08-05</date><risdate>2019</risdate><volume>5</volume><issue>1</issue><spage>125</spage><epage>13</epage><pages>125-13</pages><artnum>125</artnum><issn>2058-7716</issn><eissn>2058-7716</eissn><abstract>Breast cancer is the most common malignant tumor in women, and progress toward long-term survival has stagnated. Pristimerin, a natural quinonemethide triterpenoid, exhibits potential anti-tumor effects on various cancers. However, the underlying mechanism remains poorly understood. In this study, we found that pristimerin reduced the viability of breast cancer cells in vitro and the growth of xenografts in vivo, and these reductions were accompanied by thioredoxin-1 (Trx-1) inhibition and ASK1 and JNK activation. The results showed that pristimerin inhibited cell cycle progression and triggered cell apoptosis and autophagy. Furthermore, we found that the generation of reactive oxygen species (ROS) was a critical mediator in pristimerin-induced cell death. Enhanced ROS generation by pristimerin activated the ASK1/JNK signaling pathway. Inhibition of ROS with N-acetyl cysteine (NAC) significantly decreased pristimerin-induced cell death by inhibiting the phosphorylation of ASK1 and JNK. Taken together, these results suggest a critical role for the ROS/ASK1/JNK pathway in the anticancer activity of pristimerin.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31396402</pmid><doi>10.1038/s41420-019-0208-0</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 631/154/436 631/67/1347 Acetylcysteine Antitumor activity Apoptosis Autophagy Biochemistry Biomedical and Life Sciences Breast cancer Cell Biology Cell cycle Cell Cycle Analysis Cell death Life Sciences MAP kinase Phagocytosis Phosphorylation Reactive oxygen species Signal transduction Stem Cells Thioredoxin Xenografts |
| title | Pristimerin induces apoptosis and autophagy via activation of ROS/ASK1/JNK pathway in human breast cancer in vitro and in vivo |
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