UNBS5162 as a novel naphthalimide holds efficacy in human gastric carcinoma cell behaviors mediated by AKT/ERK signaling pathway
Purpose: Studies have determined that UNBS5162, recognized as a new naphthalimide, holds inhibitory effects in prostate and breast tumors; however, its functional implication on gastric carcinoma is currently undetermined. Based on this, this study designed to assess the functional role of it on hum...
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Veröffentlicht in: | Drug development and industrial pharmacy 2019-08, Vol.45 (8), p.1306-1312 |
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description | Purpose: Studies have determined that UNBS5162, recognized as a new naphthalimide, holds inhibitory effects in prostate and breast tumors; however, its functional implication on gastric carcinoma is currently undetermined. Based on this, this study designed to assess the functional role of it on human gastric carcinoma and underlying mechanism of action.
Methods: Cell counting kit-8 (CCK-8) assay, transwell assay, and flow cytometry were used to assess capabilities of SGC-7901 cell proliferation, invasion/migration, and apoptosis, respectively. Moreover, western blot was performed to determine the relative expression of protein related to autophagy and protein kinase B (AKT)/extracellular regulated protein kinases (ERK) signaling pathway.
Results: We found SGC-7901 cells proliferation, invasion, and migration were significantly inhibited after treatment of UNBS5162. Moreover, the expression levels of anti-apoptotic protein Bcl-2 decreased while the expression of pro-apoptotic protein active caspase 3 and Bax increased concurrently after UNBS5162 stimulation. Further, upregulated LC3 II/I and Beclin-1 and downregulated P62 were induced by UNBS5162 addition. Mechanically, the ratios of phosphorylated-(p-)AKT/AKT, p-mammalian target of rapamycin (mTOR)/mTOR, and p-ERK/ERK were hampered by UNBS5162 application.
Conclusion: UNBS5162 could restrain gastric carcinoma cell proliferation, invasion, and migration, which maybe induced by enhancement of apoptosis, autophagy manipulated through AKT/ERK signaling pathway. |
doi_str_mv | 10.1080/03639045.2019.1607870 |
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Methods: Cell counting kit-8 (CCK-8) assay, transwell assay, and flow cytometry were used to assess capabilities of SGC-7901 cell proliferation, invasion/migration, and apoptosis, respectively. Moreover, western blot was performed to determine the relative expression of protein related to autophagy and protein kinase B (AKT)/extracellular regulated protein kinases (ERK) signaling pathway.
Results: We found SGC-7901 cells proliferation, invasion, and migration were significantly inhibited after treatment of UNBS5162. Moreover, the expression levels of anti-apoptotic protein Bcl-2 decreased while the expression of pro-apoptotic protein active caspase 3 and Bax increased concurrently after UNBS5162 stimulation. Further, upregulated LC3 II/I and Beclin-1 and downregulated P62 were induced by UNBS5162 addition. Mechanically, the ratios of phosphorylated-(p-)AKT/AKT, p-mammalian target of rapamycin (mTOR)/mTOR, and p-ERK/ERK were hampered by UNBS5162 application.
Conclusion: UNBS5162 could restrain gastric carcinoma cell proliferation, invasion, and migration, which maybe induced by enhancement of apoptosis, autophagy manipulated through AKT/ERK signaling pathway.</description><identifier>ISSN: 0363-9045</identifier><identifier>EISSN: 1520-5762</identifier><identifier>DOI: 10.1080/03639045.2019.1607870</identifier><identifier>PMID: 30995142</identifier><language>eng</language><publisher>England: Taylor & Francis</publisher><subject>AKT/ERK ; apoptosis ; Apoptosis - drug effects ; autophagy ; Autophagy - drug effects ; Carcinoma - drug therapy ; Carcinoma - metabolism ; Cell Line, Tumor ; Cell Movement - drug effects ; Cell Proliferation - drug effects ; Down-Regulation - drug effects ; Extracellular Signal-Regulated MAP Kinases - metabolism ; gastric carcinoma ; Humans ; MAP Kinase Signaling System - drug effects ; Naphthalimides - pharmacology ; Neoplasm Invasiveness - pathology ; Proto-Oncogene Proteins c-akt - metabolism ; Signal Transduction - drug effects ; Stomach Neoplasms - drug therapy ; Stomach Neoplasms - metabolism ; TOR Serine-Threonine Kinases - metabolism ; UNBS5162 ; Up-Regulation - drug effects ; Urea - analogs & derivatives ; Urea - pharmacology</subject><ispartof>Drug development and industrial pharmacy, 2019-08, Vol.45 (8), p.1306-1312</ispartof><rights>2019 Informa UK Limited, trading as Taylor & Francis Group 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c366t-86a569f8375c8d4a433f61ea223301ca57da3aa197f0cd619be6a1ee5c968a663</citedby><cites>FETCH-LOGICAL-c366t-86a569f8375c8d4a433f61ea223301ca57da3aa197f0cd619be6a1ee5c968a663</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30995142$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Hong-Hai</creatorcontrib><creatorcontrib>Song, Xian-Xu</creatorcontrib><creatorcontrib>Liu, Bo</creatorcontrib><creatorcontrib>Yang, Wen-Ping</creatorcontrib><title>UNBS5162 as a novel naphthalimide holds efficacy in human gastric carcinoma cell behaviors mediated by AKT/ERK signaling pathway</title><title>Drug development and industrial pharmacy</title><addtitle>Drug Dev Ind Pharm</addtitle><description>Purpose: Studies have determined that UNBS5162, recognized as a new naphthalimide, holds inhibitory effects in prostate and breast tumors; however, its functional implication on gastric carcinoma is currently undetermined. Based on this, this study designed to assess the functional role of it on human gastric carcinoma and underlying mechanism of action.
Methods: Cell counting kit-8 (CCK-8) assay, transwell assay, and flow cytometry were used to assess capabilities of SGC-7901 cell proliferation, invasion/migration, and apoptosis, respectively. Moreover, western blot was performed to determine the relative expression of protein related to autophagy and protein kinase B (AKT)/extracellular regulated protein kinases (ERK) signaling pathway.
Results: We found SGC-7901 cells proliferation, invasion, and migration were significantly inhibited after treatment of UNBS5162. Moreover, the expression levels of anti-apoptotic protein Bcl-2 decreased while the expression of pro-apoptotic protein active caspase 3 and Bax increased concurrently after UNBS5162 stimulation. Further, upregulated LC3 II/I and Beclin-1 and downregulated P62 were induced by UNBS5162 addition. Mechanically, the ratios of phosphorylated-(p-)AKT/AKT, p-mammalian target of rapamycin (mTOR)/mTOR, and p-ERK/ERK were hampered by UNBS5162 application.
Conclusion: UNBS5162 could restrain gastric carcinoma cell proliferation, invasion, and migration, which maybe induced by enhancement of apoptosis, autophagy manipulated through AKT/ERK signaling pathway.</description><subject>AKT/ERK</subject><subject>apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>autophagy</subject><subject>Autophagy - drug effects</subject><subject>Carcinoma - drug therapy</subject><subject>Carcinoma - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Down-Regulation - drug effects</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>gastric carcinoma</subject><subject>Humans</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Naphthalimides - pharmacology</subject><subject>Neoplasm Invasiveness - pathology</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Stomach Neoplasms - drug therapy</subject><subject>Stomach Neoplasms - metabolism</subject><subject>TOR Serine-Threonine Kinases - metabolism</subject><subject>UNBS5162</subject><subject>Up-Regulation - drug effects</subject><subject>Urea - analogs & derivatives</subject><subject>Urea - pharmacology</subject><issn>0363-9045</issn><issn>1520-5762</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kLtu3DAQRYnAQbx-fEIClm605kOkxM4POE5gIwH8qIlZilzRkMg1qbWhLp8eCbtOmWqaM_fOHIS-UrKkpCbnhEuuSCmWjFC1pJJUdUU-oQUVjBSikuwALWammKFDdJTzCyGUKSG-oENOlBK0ZAv05_nX1aOgkmHIGHCIb7bDATbt0ELne99Y3Mauydg65w2YEfuA220PAa8hD8kbbCAZH2IP2NiuwyvbwpuPKePeNh4G2-DViC_vns5vHu5w9uswBYc13sDQvsN4gj476LI93c9j9Pz95un6R3H_-_bn9eV9YbiUQ1FLEFK5mlfC1E0JJedOUguMcU6oAVE1wAGoqhwxjaRqZSVQa4VRsgYp-TE62-VuUnzd2jzo3uf5YAg2brNmjFLOqrJSEyp2qEkx52Sd3iTfQxo1JXqWrz_k61m-3suf9r7tK7ar6fd_Wx-2J-BiB_jgYurhPaau0QOMXUwuQTA-a_7_jr8iT5Nq</recordid><startdate>20190803</startdate><enddate>20190803</enddate><creator>Li, Hong-Hai</creator><creator>Song, Xian-Xu</creator><creator>Liu, Bo</creator><creator>Yang, Wen-Ping</creator><general>Taylor & Francis</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></search><sort><creationdate>20190803</creationdate><title>UNBS5162 as a novel naphthalimide holds efficacy in human gastric carcinoma cell behaviors mediated by AKT/ERK signaling pathway</title><author>Li, Hong-Hai ; Song, Xian-Xu ; Liu, Bo ; Yang, Wen-Ping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c366t-86a569f8375c8d4a433f61ea223301ca57da3aa197f0cd619be6a1ee5c968a663</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>AKT/ERK</topic><topic>apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>autophagy</topic><topic>Autophagy - drug effects</topic><topic>Carcinoma - drug therapy</topic><topic>Carcinoma - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Down-Regulation - drug effects</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>gastric carcinoma</topic><topic>Humans</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Naphthalimides - pharmacology</topic><topic>Neoplasm Invasiveness - pathology</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>Stomach Neoplasms - drug therapy</topic><topic>Stomach Neoplasms - metabolism</topic><topic>TOR Serine-Threonine Kinases - metabolism</topic><topic>UNBS5162</topic><topic>Up-Regulation - drug effects</topic><topic>Urea - analogs & derivatives</topic><topic>Urea - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Hong-Hai</creatorcontrib><creatorcontrib>Song, Xian-Xu</creatorcontrib><creatorcontrib>Liu, Bo</creatorcontrib><creatorcontrib>Yang, Wen-Ping</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><jtitle>Drug development and industrial pharmacy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Hong-Hai</au><au>Song, Xian-Xu</au><au>Liu, Bo</au><au>Yang, Wen-Ping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>UNBS5162 as a novel naphthalimide holds efficacy in human gastric carcinoma cell behaviors mediated by AKT/ERK signaling pathway</atitle><jtitle>Drug development and industrial pharmacy</jtitle><addtitle>Drug Dev Ind Pharm</addtitle><date>2019-08-03</date><risdate>2019</risdate><volume>45</volume><issue>8</issue><spage>1306</spage><epage>1312</epage><pages>1306-1312</pages><issn>0363-9045</issn><eissn>1520-5762</eissn><abstract>Purpose: Studies have determined that UNBS5162, recognized as a new naphthalimide, holds inhibitory effects in prostate and breast tumors; however, its functional implication on gastric carcinoma is currently undetermined. Based on this, this study designed to assess the functional role of it on human gastric carcinoma and underlying mechanism of action.
Methods: Cell counting kit-8 (CCK-8) assay, transwell assay, and flow cytometry were used to assess capabilities of SGC-7901 cell proliferation, invasion/migration, and apoptosis, respectively. Moreover, western blot was performed to determine the relative expression of protein related to autophagy and protein kinase B (AKT)/extracellular regulated protein kinases (ERK) signaling pathway.
Results: We found SGC-7901 cells proliferation, invasion, and migration were significantly inhibited after treatment of UNBS5162. Moreover, the expression levels of anti-apoptotic protein Bcl-2 decreased while the expression of pro-apoptotic protein active caspase 3 and Bax increased concurrently after UNBS5162 stimulation. Further, upregulated LC3 II/I and Beclin-1 and downregulated P62 were induced by UNBS5162 addition. Mechanically, the ratios of phosphorylated-(p-)AKT/AKT, p-mammalian target of rapamycin (mTOR)/mTOR, and p-ERK/ERK were hampered by UNBS5162 application.
Conclusion: UNBS5162 could restrain gastric carcinoma cell proliferation, invasion, and migration, which maybe induced by enhancement of apoptosis, autophagy manipulated through AKT/ERK signaling pathway.</abstract><cop>England</cop><pub>Taylor & Francis</pub><pmid>30995142</pmid><doi>10.1080/03639045.2019.1607870</doi><tpages>7</tpages></addata></record> |
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subjects | AKT/ERK apoptosis Apoptosis - drug effects autophagy Autophagy - drug effects Carcinoma - drug therapy Carcinoma - metabolism Cell Line, Tumor Cell Movement - drug effects Cell Proliferation - drug effects Down-Regulation - drug effects Extracellular Signal-Regulated MAP Kinases - metabolism gastric carcinoma Humans MAP Kinase Signaling System - drug effects Naphthalimides - pharmacology Neoplasm Invasiveness - pathology Proto-Oncogene Proteins c-akt - metabolism Signal Transduction - drug effects Stomach Neoplasms - drug therapy Stomach Neoplasms - metabolism TOR Serine-Threonine Kinases - metabolism UNBS5162 Up-Regulation - drug effects Urea - analogs & derivatives Urea - pharmacology |
title | UNBS5162 as a novel naphthalimide holds efficacy in human gastric carcinoma cell behaviors mediated by AKT/ERK signaling pathway |
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