Disulfiram/Copper induces antitumor activity against gastric cancer via the ROS/MAPK and NPL4 pathways
Disulfiram (DSF) is an anti-alcoholism medication with superior antitumor activity and clinical safety; its antitumor mechanisms in gastric cancer (GC) have not been fully explored. In the present work, low nontoxic concentrations of copper (Cu) ions substantially enhanced DSF's antitumor activ...
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| Veröffentlicht in: | Bioengineered 2022-03, Vol.13 (3), p.6579-6589 |
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| container_title | Bioengineered |
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| creator | Liu, Yao Guan, Xin Wang, Meiling Wang, Naixue Chen, Yutong Li, Baolei Xu, Zhuxuan Fu, Fangwei Du, Cheng Zheng, Zhendong |
| description | Disulfiram (DSF) is an anti-alcoholism medication with superior antitumor activity and clinical safety; its antitumor mechanisms in gastric cancer (GC) have not been fully explored. In the present work, low nontoxic concentrations of copper (Cu) ions substantially enhanced DSF's antitumor activity, inhibiting the proliferation and growth of GC cell lines. DSF/Cu elevated the generation of reactive oxygen species (ROS), and apoptosis was induced in an ROS-dependent manner. This process might involve primary inhibition GC by DSF/Cu through induction of apoptosis via the ROS/mitogen-activated protein kinase pathway. Disordering transportation of ubiquitinated protein may also fuel the process. In summary, we found that DSF exerts antitumor effects on GC. DSF/Cu should be considered as adjunctive therapy for GC. |
| doi_str_mv | 10.1080/21655979.2022.2038434 |
| format | Article |
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In the present work, low nontoxic concentrations of copper (Cu) ions substantially enhanced DSF's antitumor activity, inhibiting the proliferation and growth of GC cell lines. DSF/Cu elevated the generation of reactive oxygen species (ROS), and apoptosis was induced in an ROS-dependent manner. This process might involve primary inhibition GC by DSF/Cu through induction of apoptosis via the ROS/mitogen-activated protein kinase pathway. Disordering transportation of ubiquitinated protein may also fuel the process. In summary, we found that DSF exerts antitumor effects on GC. DSF/Cu should be considered as adjunctive therapy for GC.</description><identifier>ISSN: 2165-5979</identifier><identifier>EISSN: 2165-5987</identifier><identifier>DOI: 10.1080/21655979.2022.2038434</identifier><identifier>PMID: 35290151</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>Cell Line, Tumor ; Copper - pharmacology ; Disulfiram ; Disulfiram - pharmacology ; Disulfiram - therapeutic use ; gastric cancer ; Humans ; nuclear protein localization protein 4 ; reactive oxygen species ; Reactive Oxygen Species - metabolism ; Research Paper ; Stomach Neoplasms - drug therapy ; ubiquitinated protein</subject><ispartof>Bioengineered, 2022-03, Vol.13 (3), p.6579-6589</ispartof><rights>2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2022</rights><rights>2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2022 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c468t-d6f5a3470bb7983cae47ec00ff9dfd404dcca0832b8786e0f54d77263a78e7a23</citedby><cites>FETCH-LOGICAL-c468t-d6f5a3470bb7983cae47ec00ff9dfd404dcca0832b8786e0f54d77263a78e7a23</cites><orcidid>0000-0002-8398-7175</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278967/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278967/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27479,27901,27902,53766,53768,59116,59117</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35290151$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Yao</creatorcontrib><creatorcontrib>Guan, Xin</creatorcontrib><creatorcontrib>Wang, Meiling</creatorcontrib><creatorcontrib>Wang, Naixue</creatorcontrib><creatorcontrib>Chen, Yutong</creatorcontrib><creatorcontrib>Li, Baolei</creatorcontrib><creatorcontrib>Xu, Zhuxuan</creatorcontrib><creatorcontrib>Fu, Fangwei</creatorcontrib><creatorcontrib>Du, Cheng</creatorcontrib><creatorcontrib>Zheng, Zhendong</creatorcontrib><title>Disulfiram/Copper induces antitumor activity against gastric cancer via the ROS/MAPK and NPL4 pathways</title><title>Bioengineered</title><addtitle>Bioengineered</addtitle><description>Disulfiram (DSF) is an anti-alcoholism medication with superior antitumor activity and clinical safety; its antitumor mechanisms in gastric cancer (GC) have not been fully explored. In the present work, low nontoxic concentrations of copper (Cu) ions substantially enhanced DSF's antitumor activity, inhibiting the proliferation and growth of GC cell lines. DSF/Cu elevated the generation of reactive oxygen species (ROS), and apoptosis was induced in an ROS-dependent manner. This process might involve primary inhibition GC by DSF/Cu through induction of apoptosis via the ROS/mitogen-activated protein kinase pathway. Disordering transportation of ubiquitinated protein may also fuel the process. In summary, we found that DSF exerts antitumor effects on GC. DSF/Cu should be considered as adjunctive therapy for GC.</description><subject>Cell Line, Tumor</subject><subject>Copper - pharmacology</subject><subject>Disulfiram</subject><subject>Disulfiram - pharmacology</subject><subject>Disulfiram - therapeutic use</subject><subject>gastric cancer</subject><subject>Humans</subject><subject>nuclear protein localization protein 4</subject><subject>reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Research Paper</subject><subject>Stomach Neoplasms - drug therapy</subject><subject>ubiquitinated protein</subject><issn>2165-5979</issn><issn>2165-5987</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><sourceid>EIF</sourceid><recordid>eNp9kUtvGyEUhVHVqonS_IRWLLtxzPAYYFM1ch-p6jZRH2t0zYBNNTNMgHHkf5-x7FjtphtAl3POvbofQq8rclURRea0qoXQUl9RQul0MMUZf4bO9_WZ0Eo-P72lPkOXOf8hhFSEcSHVS3TGBNWkEtU58h9CHlsfEnTzRRwGl3Dom9G6jKEvoYxdTBhsCdtQdhjWEPpc8BpyScFiC72dHNsAuGwc_nH7c_7t-u7rZG3w97slxwOUzQPs8iv0wkOb3eXxvkC_P338tbiZLW8_f1lcL2eW16rMmtoLYFyS1UpqxSw4Lp0lxHvd-IYT3lgLRDG6UlLVjnjBGylpzUAqJ4GyC_TukDuMq8411vUlQWuGFDpIOxMhmH9_-rAx67g1mkqlazkFvD0GpHg_ulxMF7J1bQu9i2M2tOaEcF1zPknFQWpTzDk5f2pTEbPHZJ4wmT0mc8Q0-d78PePJ9QRlErw_CELvY-rgIaa2MQV2bUw-TSsP2bD_93gEClGjJQ</recordid><startdate>20220301</startdate><enddate>20220301</enddate><creator>Liu, Yao</creator><creator>Guan, Xin</creator><creator>Wang, Meiling</creator><creator>Wang, Naixue</creator><creator>Chen, Yutong</creator><creator>Li, Baolei</creator><creator>Xu, Zhuxuan</creator><creator>Fu, Fangwei</creator><creator>Du, Cheng</creator><creator>Zheng, Zhendong</creator><general>Taylor & Francis</general><scope>0YH</scope><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><orcidid>https://orcid.org/0000-0002-8398-7175</orcidid></search><sort><creationdate>20220301</creationdate><title>Disulfiram/Copper induces antitumor activity against gastric cancer via the ROS/MAPK and NPL4 pathways</title><author>Liu, Yao ; Guan, Xin ; Wang, Meiling ; Wang, Naixue ; Chen, Yutong ; Li, Baolei ; Xu, Zhuxuan ; Fu, Fangwei ; Du, Cheng ; Zheng, Zhendong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c468t-d6f5a3470bb7983cae47ec00ff9dfd404dcca0832b8786e0f54d77263a78e7a23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Cell Line, Tumor</topic><topic>Copper - pharmacology</topic><topic>Disulfiram</topic><topic>Disulfiram - pharmacology</topic><topic>Disulfiram - therapeutic use</topic><topic>gastric cancer</topic><topic>Humans</topic><topic>nuclear protein localization protein 4</topic><topic>reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Research Paper</topic><topic>Stomach Neoplasms - drug therapy</topic><topic>ubiquitinated protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Yao</creatorcontrib><creatorcontrib>Guan, Xin</creatorcontrib><creatorcontrib>Wang, Meiling</creatorcontrib><creatorcontrib>Wang, Naixue</creatorcontrib><creatorcontrib>Chen, Yutong</creatorcontrib><creatorcontrib>Li, Baolei</creatorcontrib><creatorcontrib>Xu, Zhuxuan</creatorcontrib><creatorcontrib>Fu, Fangwei</creatorcontrib><creatorcontrib>Du, Cheng</creatorcontrib><creatorcontrib>Zheng, Zhendong</creatorcontrib><collection>Taylor & Francis Open Access</collection><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>Bioengineered</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Yao</au><au>Guan, Xin</au><au>Wang, Meiling</au><au>Wang, Naixue</au><au>Chen, Yutong</au><au>Li, Baolei</au><au>Xu, Zhuxuan</au><au>Fu, Fangwei</au><au>Du, Cheng</au><au>Zheng, Zhendong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Disulfiram/Copper induces antitumor activity against gastric cancer via the ROS/MAPK and NPL4 pathways</atitle><jtitle>Bioengineered</jtitle><addtitle>Bioengineered</addtitle><date>2022-03-01</date><risdate>2022</risdate><volume>13</volume><issue>3</issue><spage>6579</spage><epage>6589</epage><pages>6579-6589</pages><issn>2165-5979</issn><eissn>2165-5987</eissn><abstract>Disulfiram (DSF) is an anti-alcoholism medication with superior antitumor activity and clinical safety; its antitumor mechanisms in gastric cancer (GC) have not been fully explored. In the present work, low nontoxic concentrations of copper (Cu) ions substantially enhanced DSF's antitumor activity, inhibiting the proliferation and growth of GC cell lines. DSF/Cu elevated the generation of reactive oxygen species (ROS), and apoptosis was induced in an ROS-dependent manner. This process might involve primary inhibition GC by DSF/Cu through induction of apoptosis via the ROS/mitogen-activated protein kinase pathway. Disordering transportation of ubiquitinated protein may also fuel the process. In summary, we found that DSF exerts antitumor effects on GC. DSF/Cu should be considered as adjunctive therapy for GC.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>35290151</pmid><doi>10.1080/21655979.2022.2038434</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-8398-7175</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Cell Line, Tumor Copper - pharmacology Disulfiram Disulfiram - pharmacology Disulfiram - therapeutic use gastric cancer Humans nuclear protein localization protein 4 reactive oxygen species Reactive Oxygen Species - metabolism Research Paper Stomach Neoplasms - drug therapy ubiquitinated protein |
| title | Disulfiram/Copper induces antitumor activity against gastric cancer via the ROS/MAPK and NPL4 pathways |
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