Berberine regulates the Notch1/PTEN/PI3K/AKT/mTOR pathway and acts synergistically with 17-AAG and SAHA in SW480 colon cancer cells
Berberine (BBR) is used to treat diarrhoea and gastroenteritis in the clinic. It was found to have anticolon cancer effects. To study the anticolon cancer mechanism of BBR by connectivity map (CMAP) analysis. CMAP based mechanistic prediction was conducted by comparing gene expression profiles of 10...
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description | Berberine (BBR) is used to treat diarrhoea and gastroenteritis in the clinic. It was found to have anticolon cancer effects.
To study the anticolon cancer mechanism of BBR by connectivity map (CMAP) analysis.
CMAP based mechanistic prediction was conducted by comparing gene expression profiles of 10 μM BBR treated MCF-7 cells with that of clinical drugs such as helveticoside, ianatoside C, pyrvinium, gossypol and trifluoperazine. The treatment time was 12 h and two biological replications were performed. The DMSO-treated cells were selected as a control. The interaction between 100 μM BBR and target protein was measured by cellular thermal shift assay. The protein expression of 1-9 μM BBR treated SW480 cells were measured by WB assay. Apoptosis, cell cycle arrest, mitochondrial membrane potential (MMP) of 1-9 μM BBR treated SW480 cells were measured by flow cytometry and Hoechst 33342 staining methods.
CMAP analysis found 14 Hsp90, HDAC, PI3K or mTOR protein inhibitors have similar functions with BBR. The experiments showed that BBR inhibited SW480 cells proliferation with IC
50
of 3.436 μM, induced apoptosis, autophage, MMP depolarization and arrested G1 phase of cell cycle at 1.0 μM. BBR dose-dependently up-regulated PTEN, while inhibited Notch1, PI3K, Akt and mTOR proteins at 1.0-9.0 μM (p |
doi_str_mv | 10.1080/13880209.2020.1865407 |
format | Article |
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To study the anticolon cancer mechanism of BBR by connectivity map (CMAP) analysis.
CMAP based mechanistic prediction was conducted by comparing gene expression profiles of 10 μM BBR treated MCF-7 cells with that of clinical drugs such as helveticoside, ianatoside C, pyrvinium, gossypol and trifluoperazine. The treatment time was 12 h and two biological replications were performed. The DMSO-treated cells were selected as a control. The interaction between 100 μM BBR and target protein was measured by cellular thermal shift assay. The protein expression of 1-9 μM BBR treated SW480 cells were measured by WB assay. Apoptosis, cell cycle arrest, mitochondrial membrane potential (MMP) of 1-9 μM BBR treated SW480 cells were measured by flow cytometry and Hoechst 33342 staining methods.
CMAP analysis found 14 Hsp90, HDAC, PI3K or mTOR protein inhibitors have similar functions with BBR. The experiments showed that BBR inhibited SW480 cells proliferation with IC
50
of 3.436 μM, induced apoptosis, autophage, MMP depolarization and arrested G1 phase of cell cycle at 1.0 μM. BBR dose-dependently up-regulated PTEN, while inhibited Notch1, PI3K, Akt and mTOR proteins at 1.0-9.0 μM (p < 0.05). BBR also acted synergistically with Hsp90 and HDAC inhibitor (0.01 μM) in SW480 cells at 0.5 and 1.0 μM.
The integrative gene expression-based chemical genomic method using CMAP analysis may be applicable for mechanistic studies of other multi-targets drugs.</description><identifier>ISSN: 1388-0209</identifier><identifier>EISSN: 1744-5116</identifier><identifier>DOI: 10.1080/13880209.2020.1865407</identifier><identifier>PMID: 33417512</identifier><language>eng</language><publisher>England: Taylor & Francis</publisher><subject>1-Phosphatidylinositol 3-kinase ; AKT protein ; Apoptosis ; Berberine ; Cancer ; Cell cycle ; Cell proliferation ; Colon cancer ; Colorectal cancer ; Connectivity map ; Depolarization ; Diarrhea ; Flow cytometry ; G1 phase ; Gastroenteritis ; Gene expression ; Gossypol ; Histone deacetylase ; Hsp90 protein ; mechanism ; Membrane potential ; Mitochondria ; Notch1 protein ; Proteins ; PTEN protein ; synergistic effect ; TOR protein ; Trifluoperazine</subject><ispartof>Pharmaceutical biology, 2021-01, Vol.59 (1), p.21-30</ispartof><rights>2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2021</rights><rights>2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This work is licensed under the Creative Commons Attribution License 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><rights>2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2021 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c562t-71e1d3ed96acf9af3efad69322ae04b67c57b1475d257c5be09853e5e274b0163</citedby><cites>FETCH-LOGICAL-c562t-71e1d3ed96acf9af3efad69322ae04b67c57b1475d257c5be09853e5e274b0163</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/PMC7808376/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808376/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,27483,27905,27906,53772,53774,59122,59123</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33417512$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Ge</creatorcontrib><creatorcontrib>Zhang, Chuang</creatorcontrib><creatorcontrib>Liang, Wei</creatorcontrib><creatorcontrib>Zhang, Yanbing</creatorcontrib><creatorcontrib>Shen, Yunheng</creatorcontrib><creatorcontrib>Tian, Xinhui</creatorcontrib><title>Berberine regulates the Notch1/PTEN/PI3K/AKT/mTOR pathway and acts synergistically with 17-AAG and SAHA in SW480 colon cancer cells</title><title>Pharmaceutical biology</title><addtitle>Pharm Biol</addtitle><description>Berberine (BBR) is used to treat diarrhoea and gastroenteritis in the clinic. It was found to have anticolon cancer effects.
To study the anticolon cancer mechanism of BBR by connectivity map (CMAP) analysis.
CMAP based mechanistic prediction was conducted by comparing gene expression profiles of 10 μM BBR treated MCF-7 cells with that of clinical drugs such as helveticoside, ianatoside C, pyrvinium, gossypol and trifluoperazine. The treatment time was 12 h and two biological replications were performed. The DMSO-treated cells were selected as a control. The interaction between 100 μM BBR and target protein was measured by cellular thermal shift assay. The protein expression of 1-9 μM BBR treated SW480 cells were measured by WB assay. Apoptosis, cell cycle arrest, mitochondrial membrane potential (MMP) of 1-9 μM BBR treated SW480 cells were measured by flow cytometry and Hoechst 33342 staining methods.
CMAP analysis found 14 Hsp90, HDAC, PI3K or mTOR protein inhibitors have similar functions with BBR. The experiments showed that BBR inhibited SW480 cells proliferation with IC
50
of 3.436 μM, induced apoptosis, autophage, MMP depolarization and arrested G1 phase of cell cycle at 1.0 μM. BBR dose-dependently up-regulated PTEN, while inhibited Notch1, PI3K, Akt and mTOR proteins at 1.0-9.0 μM (p < 0.05). BBR also acted synergistically with Hsp90 and HDAC inhibitor (0.01 μM) in SW480 cells at 0.5 and 1.0 μM.
The integrative gene expression-based chemical genomic method using CMAP analysis may be applicable for mechanistic studies of other multi-targets drugs.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>AKT protein</subject><subject>Apoptosis</subject><subject>Berberine</subject><subject>Cancer</subject><subject>Cell cycle</subject><subject>Cell proliferation</subject><subject>Colon cancer</subject><subject>Colorectal cancer</subject><subject>Connectivity map</subject><subject>Depolarization</subject><subject>Diarrhea</subject><subject>Flow cytometry</subject><subject>G1 phase</subject><subject>Gastroenteritis</subject><subject>Gene expression</subject><subject>Gossypol</subject><subject>Histone deacetylase</subject><subject>Hsp90 protein</subject><subject>mechanism</subject><subject>Membrane potential</subject><subject>Mitochondria</subject><subject>Notch1 protein</subject><subject>Proteins</subject><subject>PTEN protein</subject><subject>synergistic effect</subject><subject>TOR protein</subject><subject>Trifluoperazine</subject><issn>1388-0209</issn><issn>1744-5116</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>DOA</sourceid><recordid>eNp9kk1vEzEQhlcIREvhJ4Ascd7En-vdC2KpShu1aisaxNHyemeTjZx1ajtEOfeP12nSil642CP7mXdmNG-WfSZ4RHCJx4SVJaa4GtF0jkhZCI7lm-yYSM5zQUjxNsWJyXfQUfYhhAXGWDAm3mdHjHEiBaHH2cMP8A34fgDkYba2OkJAcQ7o2kUzJ-Pb6dn1-HbCLsf15XS8nN78Qisd5xu9RXpokTYxoLAdwM_6EHujrd2iTR_niMi8rs-foLv6okb9gO7-8BIj46wbkNGDAY8MWBs-Zu86bQN8Otwn2e-fZ9PTi_zq5nxyWl_lRhQ05pIAaRm0VaFNV-mOQafbomKUasC8KaQRsiFcipaKFDeAq1IwEEAlbzAp2Ek22eu2Ti_UyvdL7bfK6V49PTg_U9qnISyoCjCWXZdyOeeFaTTFkpeNAdYQY3iVtL7ttVbrZgmtgSF6bV-Jvv4Z-rmaub9KlrhkctfM14OAd_drCFEt3NoPaX5Fi4oQTipKEiX2lPEuBA_dSwWC1c4H6tkHaucDdfBByvvyb3svWc-LT8D3PdAPnfNLvXHetirqrXW-82k5fVDs_zUeAYr6wEw</recordid><startdate>20210101</startdate><enddate>20210101</enddate><creator>Li, Ge</creator><creator>Zhang, Chuang</creator><creator>Liang, Wei</creator><creator>Zhang, Yanbing</creator><creator>Shen, Yunheng</creator><creator>Tian, Xinhui</creator><general>Taylor & Francis</general><general>Taylor & Francis Ltd</general><general>Taylor & Francis Group</general><scope>0YH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20210101</creationdate><title>Berberine regulates the Notch1/PTEN/PI3K/AKT/mTOR pathway and acts synergistically with 17-AAG and SAHA in SW480 colon cancer cells</title><author>Li, Ge ; Zhang, Chuang ; Liang, Wei ; Zhang, Yanbing ; Shen, Yunheng ; Tian, Xinhui</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c562t-71e1d3ed96acf9af3efad69322ae04b67c57b1475d257c5be09853e5e274b0163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>AKT protein</topic><topic>Apoptosis</topic><topic>Berberine</topic><topic>Cancer</topic><topic>Cell cycle</topic><topic>Cell proliferation</topic><topic>Colon cancer</topic><topic>Colorectal cancer</topic><topic>Connectivity map</topic><topic>Depolarization</topic><topic>Diarrhea</topic><topic>Flow cytometry</topic><topic>G1 phase</topic><topic>Gastroenteritis</topic><topic>Gene expression</topic><topic>Gossypol</topic><topic>Histone deacetylase</topic><topic>Hsp90 protein</topic><topic>mechanism</topic><topic>Membrane potential</topic><topic>Mitochondria</topic><topic>Notch1 protein</topic><topic>Proteins</topic><topic>PTEN protein</topic><topic>synergistic effect</topic><topic>TOR protein</topic><topic>Trifluoperazine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Ge</creatorcontrib><creatorcontrib>Zhang, Chuang</creatorcontrib><creatorcontrib>Liang, Wei</creatorcontrib><creatorcontrib>Zhang, Yanbing</creatorcontrib><creatorcontrib>Shen, Yunheng</creatorcontrib><creatorcontrib>Tian, Xinhui</creatorcontrib><collection>Taylor & Francis Open Access</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>Technology Research Database</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>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content 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>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Pharmaceutical biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Ge</au><au>Zhang, Chuang</au><au>Liang, Wei</au><au>Zhang, Yanbing</au><au>Shen, Yunheng</au><au>Tian, Xinhui</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Berberine regulates the Notch1/PTEN/PI3K/AKT/mTOR pathway and acts synergistically with 17-AAG and SAHA in SW480 colon cancer cells</atitle><jtitle>Pharmaceutical biology</jtitle><addtitle>Pharm Biol</addtitle><date>2021-01-01</date><risdate>2021</risdate><volume>59</volume><issue>1</issue><spage>21</spage><epage>30</epage><pages>21-30</pages><issn>1388-0209</issn><eissn>1744-5116</eissn><abstract>Berberine (BBR) is used to treat diarrhoea and gastroenteritis in the clinic. It was found to have anticolon cancer effects.
To study the anticolon cancer mechanism of BBR by connectivity map (CMAP) analysis.
CMAP based mechanistic prediction was conducted by comparing gene expression profiles of 10 μM BBR treated MCF-7 cells with that of clinical drugs such as helveticoside, ianatoside C, pyrvinium, gossypol and trifluoperazine. The treatment time was 12 h and two biological replications were performed. The DMSO-treated cells were selected as a control. The interaction between 100 μM BBR and target protein was measured by cellular thermal shift assay. The protein expression of 1-9 μM BBR treated SW480 cells were measured by WB assay. Apoptosis, cell cycle arrest, mitochondrial membrane potential (MMP) of 1-9 μM BBR treated SW480 cells were measured by flow cytometry and Hoechst 33342 staining methods.
CMAP analysis found 14 Hsp90, HDAC, PI3K or mTOR protein inhibitors have similar functions with BBR. The experiments showed that BBR inhibited SW480 cells proliferation with IC
50
of 3.436 μM, induced apoptosis, autophage, MMP depolarization and arrested G1 phase of cell cycle at 1.0 μM. BBR dose-dependently up-regulated PTEN, while inhibited Notch1, PI3K, Akt and mTOR proteins at 1.0-9.0 μM (p < 0.05). BBR also acted synergistically with Hsp90 and HDAC inhibitor (0.01 μM) in SW480 cells at 0.5 and 1.0 μM.
The integrative gene expression-based chemical genomic method using CMAP analysis may be applicable for mechanistic studies of other multi-targets drugs.</abstract><cop>England</cop><pub>Taylor & Francis</pub><pmid>33417512</pmid><doi>10.1080/13880209.2020.1865407</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | 1-Phosphatidylinositol 3-kinase AKT protein Apoptosis Berberine Cancer Cell cycle Cell proliferation Colon cancer Colorectal cancer Connectivity map Depolarization Diarrhea Flow cytometry G1 phase Gastroenteritis Gene expression Gossypol Histone deacetylase Hsp90 protein mechanism Membrane potential Mitochondria Notch1 protein Proteins PTEN protein synergistic effect TOR protein Trifluoperazine |
title | Berberine regulates the Notch1/PTEN/PI3K/AKT/mTOR pathway and acts synergistically with 17-AAG and SAHA in SW480 colon cancer cells |
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