The synthetic antihyperlipidemic drug potassium piperate selectively kills breast cancer cells through inhibiting G1-S-phase transition and inducing apoptosis
Piper longum L. is a well-known traditional antihyperlipidemic medicine in China, containing medicinal constituents of piperine, pipernonaline and piperlonguminine in its fruit. However, the antitumor properties of these constituents have not yet been studied. We found that potassium piperate (GBK),...
Gespeichert in:
Veröffentlicht in: | Oncotarget 2017-07, Vol.8 (29), p.47250-47268 |
---|---|
Hauptverfasser: | , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 47268 |
---|---|
container_issue | 29 |
container_start_page | 47250 |
container_title | Oncotarget |
container_volume | 8 |
creator | Fan, Lifei Cao, Xuemin Yan, Huijuan Wang, Qian Tian, Xiaoxia Zhang, Lan He, Xiaoyan Borjihan, Gereltu Morigen |
description | Piper longum L. is a well-known traditional antihyperlipidemic medicine in China, containing medicinal constituents of piperine, pipernonaline and piperlonguminine in its fruit. However, the antitumor properties of these constituents have not yet been studied. We found that potassium piperate (GBK), a derivative of piperine, inhibited proliferation of cancer cells. GBK selectively inhibited the G1-S-phase transition in breast cancer cells and the G1 arrest was correlated with induction of p27 expression, which is an inhibitor for cyclin-dependent kinases, and inhibition of cyclin A, cyclin E and cyclin B expression. Moreover, GBK treatment led to a downregulation of the mini-chromosome maintenance protein expression and induction of mitochondrial-dependent cell apoptosis in breast cancer cells. Our results also suggested that GBK might also inhibit cancer cell proliferation through epigenetic signaling pathways. A synergistic effect in inhibition of cancer cell proliferation was found when GBK was combined with chemotherapy medicines etoposide phosphate or cisplatin at middle or low doses in vitro. These results show that GBK is a novel potential anti-breast cancer drug that inhibits cell proliferation and promotes cell apoptosis. |
doi_str_mv | 10.18632/oncotarget.16872 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5564562</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1895278024</sourcerecordid><originalsourceid>FETCH-LOGICAL-c356t-6f3c14894f0d191295b281428fb214e128f8648e43bd7727be5d094fa8689c413</originalsourceid><addsrcrecordid>eNpVUcFu1TAQtBCIVqUfwAX5yCUldmzHviChCgpSJQ6Us-U4m8SQ2MZ2Kr2f4Vvxa0spvng1Ozuz2kHoNWkviBQdfRe8DcWkGcoFEbKnz9ApUUw1lPPu-ZP6BJ3n_KOtj7NeUvUSnVDJRN-r9hT9vlkA54MvCxRnsfHFLYcIaXXRjbBVaEz7jGN1ytntG46udk2pQ7CCLe4W1gP-6dY14yGByQVb4y0kbOGIlSWFfV6w84sbXHF-xlek-dbExWTAJRmfKxp8dR4radztkWJiiCVkl1-hF5NZM5w__Gfo-6ePN5efm-uvV18uP1w3tuOiNGLqLGFSsakdiSJU8YFKwqicBkoYkFpIwSSwbhj7nvYD8LGtbCOFVJaR7gy9v9eN-7DBaMHX1VYdk9tMOuhgnP6_492i53CrOReMC1oF3j4IpPBrh1z05vLxBMZD2LMmUnHay5aySiX3VJtCzgmmRxvS6rto9b9o9V20debN0_0eJ_4G2f0BOVCnvw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1895278024</pqid></control><display><type>article</type><title>The synthetic antihyperlipidemic drug potassium piperate selectively kills breast cancer cells through inhibiting G1-S-phase transition and inducing apoptosis</title><source>MEDLINE</source><source>PubMed Central</source><source>Free E- Journals</source><source>EZB Electronic Journals Library</source><source>PubMed Central Open Access</source><creator>Fan, Lifei ; Cao, Xuemin ; Yan, Huijuan ; Wang, Qian ; Tian, Xiaoxia ; Zhang, Lan ; He, Xiaoyan ; Borjihan, Gereltu ; Morigen</creator><creatorcontrib>Fan, Lifei ; Cao, Xuemin ; Yan, Huijuan ; Wang, Qian ; Tian, Xiaoxia ; Zhang, Lan ; He, Xiaoyan ; Borjihan, Gereltu ; Morigen</creatorcontrib><description>Piper longum L. is a well-known traditional antihyperlipidemic medicine in China, containing medicinal constituents of piperine, pipernonaline and piperlonguminine in its fruit. However, the antitumor properties of these constituents have not yet been studied. We found that potassium piperate (GBK), a derivative of piperine, inhibited proliferation of cancer cells. GBK selectively inhibited the G1-S-phase transition in breast cancer cells and the G1 arrest was correlated with induction of p27 expression, which is an inhibitor for cyclin-dependent kinases, and inhibition of cyclin A, cyclin E and cyclin B expression. Moreover, GBK treatment led to a downregulation of the mini-chromosome maintenance protein expression and induction of mitochondrial-dependent cell apoptosis in breast cancer cells. Our results also suggested that GBK might also inhibit cancer cell proliferation through epigenetic signaling pathways. A synergistic effect in inhibition of cancer cell proliferation was found when GBK was combined with chemotherapy medicines etoposide phosphate or cisplatin at middle or low doses in vitro. These results show that GBK is a novel potential anti-breast cancer drug that inhibits cell proliferation and promotes cell apoptosis.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.16872</identifier><identifier>PMID: 28467790</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Animals ; Antineoplastic Agents, Phytogenic - chemical synthesis ; Antineoplastic Agents, Phytogenic - pharmacology ; Apoptosis - drug effects ; Breast Neoplasms ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cell Survival ; Cisplatin - pharmacology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Synergism ; Etoposide - pharmacology ; Female ; G1 Phase Cell Cycle Checkpoints - drug effects ; Humans ; Hypolipidemic Agents - chemical synthesis ; Hypolipidemic Agents - pharmacology ; MCF-7 Cells ; Mice ; Piperidines - chemical synthesis ; Piperidines - pharmacology ; Reactive Oxygen Species - metabolism ; Research Paper ; Stress, Physiological ; Xenograft Model Antitumor Assays</subject><ispartof>Oncotarget, 2017-07, Vol.8 (29), p.47250-47268</ispartof><rights>Copyright: © 2017 Fan et al. 2017</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-6f3c14894f0d191295b281428fb214e128f8648e43bd7727be5d094fa8689c413</citedby><cites>FETCH-LOGICAL-c356t-6f3c14894f0d191295b281428fb214e128f8648e43bd7727be5d094fa8689c413</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/PMC5564562/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564562/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28467790$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fan, Lifei</creatorcontrib><creatorcontrib>Cao, Xuemin</creatorcontrib><creatorcontrib>Yan, Huijuan</creatorcontrib><creatorcontrib>Wang, Qian</creatorcontrib><creatorcontrib>Tian, Xiaoxia</creatorcontrib><creatorcontrib>Zhang, Lan</creatorcontrib><creatorcontrib>He, Xiaoyan</creatorcontrib><creatorcontrib>Borjihan, Gereltu</creatorcontrib><creatorcontrib>Morigen</creatorcontrib><title>The synthetic antihyperlipidemic drug potassium piperate selectively kills breast cancer cells through inhibiting G1-S-phase transition and inducing apoptosis</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>Piper longum L. is a well-known traditional antihyperlipidemic medicine in China, containing medicinal constituents of piperine, pipernonaline and piperlonguminine in its fruit. However, the antitumor properties of these constituents have not yet been studied. We found that potassium piperate (GBK), a derivative of piperine, inhibited proliferation of cancer cells. GBK selectively inhibited the G1-S-phase transition in breast cancer cells and the G1 arrest was correlated with induction of p27 expression, which is an inhibitor for cyclin-dependent kinases, and inhibition of cyclin A, cyclin E and cyclin B expression. Moreover, GBK treatment led to a downregulation of the mini-chromosome maintenance protein expression and induction of mitochondrial-dependent cell apoptosis in breast cancer cells. Our results also suggested that GBK might also inhibit cancer cell proliferation through epigenetic signaling pathways. A synergistic effect in inhibition of cancer cell proliferation was found when GBK was combined with chemotherapy medicines etoposide phosphate or cisplatin at middle or low doses in vitro. These results show that GBK is a novel potential anti-breast cancer drug that inhibits cell proliferation and promotes cell apoptosis.</description><subject>Animals</subject><subject>Antineoplastic Agents, Phytogenic - chemical synthesis</subject><subject>Antineoplastic Agents, Phytogenic - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Breast Neoplasms</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival</subject><subject>Cisplatin - pharmacology</subject><subject>Disease Models, Animal</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Synergism</subject><subject>Etoposide - pharmacology</subject><subject>Female</subject><subject>G1 Phase Cell Cycle Checkpoints - drug effects</subject><subject>Humans</subject><subject>Hypolipidemic Agents - chemical synthesis</subject><subject>Hypolipidemic Agents - pharmacology</subject><subject>MCF-7 Cells</subject><subject>Mice</subject><subject>Piperidines - chemical synthesis</subject><subject>Piperidines - pharmacology</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Research Paper</subject><subject>Stress, Physiological</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>eNpVUcFu1TAQtBCIVqUfwAX5yCUldmzHviChCgpSJQ6Us-U4m8SQ2MZ2Kr2f4Vvxa0spvng1Ozuz2kHoNWkviBQdfRe8DcWkGcoFEbKnz9ApUUw1lPPu-ZP6BJ3n_KOtj7NeUvUSnVDJRN-r9hT9vlkA54MvCxRnsfHFLYcIaXXRjbBVaEz7jGN1ytntG46udk2pQ7CCLe4W1gP-6dY14yGByQVb4y0kbOGIlSWFfV6w84sbXHF-xlek-dbExWTAJRmfKxp8dR4radztkWJiiCVkl1-hF5NZM5w__Gfo-6ePN5efm-uvV18uP1w3tuOiNGLqLGFSsakdiSJU8YFKwqicBkoYkFpIwSSwbhj7nvYD8LGtbCOFVJaR7gy9v9eN-7DBaMHX1VYdk9tMOuhgnP6_492i53CrOReMC1oF3j4IpPBrh1z05vLxBMZD2LMmUnHay5aySiX3VJtCzgmmRxvS6rto9b9o9V20debN0_0eJ_4G2f0BOVCnvw</recordid><startdate>20170718</startdate><enddate>20170718</enddate><creator>Fan, Lifei</creator><creator>Cao, Xuemin</creator><creator>Yan, Huijuan</creator><creator>Wang, Qian</creator><creator>Tian, Xiaoxia</creator><creator>Zhang, Lan</creator><creator>He, Xiaoyan</creator><creator>Borjihan, Gereltu</creator><creator>Morigen</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>20170718</creationdate><title>The synthetic antihyperlipidemic drug potassium piperate selectively kills breast cancer cells through inhibiting G1-S-phase transition and inducing apoptosis</title><author>Fan, Lifei ; Cao, Xuemin ; Yan, Huijuan ; Wang, Qian ; Tian, Xiaoxia ; Zhang, Lan ; He, Xiaoyan ; Borjihan, Gereltu ; Morigen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-6f3c14894f0d191295b281428fb214e128f8648e43bd7727be5d094fa8689c413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Antineoplastic Agents, Phytogenic - chemical synthesis</topic><topic>Antineoplastic Agents, Phytogenic - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>Breast Neoplasms</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival</topic><topic>Cisplatin - pharmacology</topic><topic>Disease Models, Animal</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Synergism</topic><topic>Etoposide - pharmacology</topic><topic>Female</topic><topic>G1 Phase Cell Cycle Checkpoints - drug effects</topic><topic>Humans</topic><topic>Hypolipidemic Agents - chemical synthesis</topic><topic>Hypolipidemic Agents - pharmacology</topic><topic>MCF-7 Cells</topic><topic>Mice</topic><topic>Piperidines - chemical synthesis</topic><topic>Piperidines - pharmacology</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Research Paper</topic><topic>Stress, Physiological</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>online_resources</toplevel><creatorcontrib>Fan, Lifei</creatorcontrib><creatorcontrib>Cao, Xuemin</creatorcontrib><creatorcontrib>Yan, Huijuan</creatorcontrib><creatorcontrib>Wang, Qian</creatorcontrib><creatorcontrib>Tian, Xiaoxia</creatorcontrib><creatorcontrib>Zhang, Lan</creatorcontrib><creatorcontrib>He, Xiaoyan</creatorcontrib><creatorcontrib>Borjihan, Gereltu</creatorcontrib><creatorcontrib>Morigen</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>Fan, Lifei</au><au>Cao, Xuemin</au><au>Yan, Huijuan</au><au>Wang, Qian</au><au>Tian, Xiaoxia</au><au>Zhang, Lan</au><au>He, Xiaoyan</au><au>Borjihan, Gereltu</au><au>Morigen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The synthetic antihyperlipidemic drug potassium piperate selectively kills breast cancer cells through inhibiting G1-S-phase transition and inducing apoptosis</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2017-07-18</date><risdate>2017</risdate><volume>8</volume><issue>29</issue><spage>47250</spage><epage>47268</epage><pages>47250-47268</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>Piper longum L. is a well-known traditional antihyperlipidemic medicine in China, containing medicinal constituents of piperine, pipernonaline and piperlonguminine in its fruit. However, the antitumor properties of these constituents have not yet been studied. We found that potassium piperate (GBK), a derivative of piperine, inhibited proliferation of cancer cells. GBK selectively inhibited the G1-S-phase transition in breast cancer cells and the G1 arrest was correlated with induction of p27 expression, which is an inhibitor for cyclin-dependent kinases, and inhibition of cyclin A, cyclin E and cyclin B expression. Moreover, GBK treatment led to a downregulation of the mini-chromosome maintenance protein expression and induction of mitochondrial-dependent cell apoptosis in breast cancer cells. Our results also suggested that GBK might also inhibit cancer cell proliferation through epigenetic signaling pathways. A synergistic effect in inhibition of cancer cell proliferation was found when GBK was combined with chemotherapy medicines etoposide phosphate or cisplatin at middle or low doses in vitro. These results show that GBK is a novel potential anti-breast cancer drug that inhibits cell proliferation and promotes cell apoptosis.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>28467790</pmid><doi>10.18632/oncotarget.16872</doi><tpages>19</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1949-2553 |
ispartof | Oncotarget, 2017-07, Vol.8 (29), p.47250-47268 |
issn | 1949-2553 1949-2553 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5564562 |
source | MEDLINE; PubMed Central; Free E- Journals; EZB Electronic Journals Library; PubMed Central Open Access |
subjects | Animals Antineoplastic Agents, Phytogenic - chemical synthesis Antineoplastic Agents, Phytogenic - pharmacology Apoptosis - drug effects Breast Neoplasms Cell Line, Tumor Cell Proliferation - drug effects Cell Survival Cisplatin - pharmacology Disease Models, Animal Dose-Response Relationship, Drug Drug Synergism Etoposide - pharmacology Female G1 Phase Cell Cycle Checkpoints - drug effects Humans Hypolipidemic Agents - chemical synthesis Hypolipidemic Agents - pharmacology MCF-7 Cells Mice Piperidines - chemical synthesis Piperidines - pharmacology Reactive Oxygen Species - metabolism Research Paper Stress, Physiological Xenograft Model Antitumor Assays |
title | The synthetic antihyperlipidemic drug potassium piperate selectively kills breast cancer cells through inhibiting G1-S-phase transition and inducing apoptosis |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-24T20%3A31%3A27IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20synthetic%20antihyperlipidemic%20drug%20potassium%20piperate%20selectively%20kills%20breast%20cancer%20cells%20through%20inhibiting%20G1-S-phase%20transition%20and%20inducing%20apoptosis&rft.jtitle=Oncotarget&rft.au=Fan,%20Lifei&rft.date=2017-07-18&rft.volume=8&rft.issue=29&rft.spage=47250&rft.epage=47268&rft.pages=47250-47268&rft.issn=1949-2553&rft.eissn=1949-2553&rft_id=info:doi/10.18632/oncotarget.16872&rft_dat=%3Cproquest_pubme%3E1895278024%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1895278024&rft_id=info:pmid/28467790&rfr_iscdi=true |