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
Hauptverfasser: Li, Hong-Hai, Song, Xian-Xu, Liu, Bo, Yang, Wen-Ping
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container_title Drug development and industrial pharmacy
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creator Li, Hong-Hai
Song, Xian-Xu
Liu, Bo
Yang, Wen-Ping
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.
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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><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 &amp; 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 &amp; 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 &amp; 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 &amp; 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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 &amp; 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 &amp; 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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