Enhancement of Cisplatin Cytotoxicity by Disulfiram Involves Activating Transcription Factor 3
Activating transcription factor 3 (ATF3), a stress-inducible gene, is a regulator of cisplatin-induced cytotoxicity, and enhancement of the ATF3 expression potentiates this cytotoxicity. ATF3 expression and its binding to the transcription target CHOP were evaluated by western blot and chromatin imm...
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| Veröffentlicht in: | Anticancer research 2012-07, Vol.32 (7), p.2679-2688 |
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| creator | O'BRIEN, Anna BARBER, Janet E. B REID, Stephanie NIKNEJAD, Nima DIMITROULAKOS, Jim |
| description | Activating transcription factor 3 (ATF3), a stress-inducible gene, is a regulator of cisplatin-induced cytotoxicity, and enhancement of the ATF3 expression potentiates this cytotoxicity.
ATF3 expression and its binding to the transcription target CHOP were evaluated by western blot and chromatin immunoprecipitation (ChIP), respectively, in a panel of five cell lines (WI38, MCF7, PC3, A549). MTT assays were employed to assess the effects of many drugs, including disulfiram, on cell viability.
ATF3 protein expression was up-regulated after cytotoxic doses of cisplatin treatment and it directly bound to the CHOP gene promoter, increasing this pro-apoptotic protein's expression. In a library screen of 1200 compounds, disulfiram, a dithiocarbamate drug, was identified as an enhancer of the cytotoxic effects of cisplatin. This increased cytotoxic action was synergistic and likely due to their ability to induce ATF3 independently.
Understanding the role of ATF3 in cisplatin-induced cytotoxicity will lead to novel therapeutic approaches that could improve this drug's efficacy. |
| format | Article |
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ATF3 expression and its binding to the transcription target CHOP were evaluated by western blot and chromatin immunoprecipitation (ChIP), respectively, in a panel of five cell lines (WI38, MCF7, PC3, A549). MTT assays were employed to assess the effects of many drugs, including disulfiram, on cell viability.
ATF3 protein expression was up-regulated after cytotoxic doses of cisplatin treatment and it directly bound to the CHOP gene promoter, increasing this pro-apoptotic protein's expression. In a library screen of 1200 compounds, disulfiram, a dithiocarbamate drug, was identified as an enhancer of the cytotoxic effects of cisplatin. This increased cytotoxic action was synergistic and likely due to their ability to induce ATF3 independently.
Understanding the role of ATF3 in cisplatin-induced cytotoxicity will lead to novel therapeutic approaches that could improve this drug's efficacy.</description><identifier>ISSN: 0250-7005</identifier><identifier>EISSN: 1791-7530</identifier><identifier>PMID: 22753726</identifier><language>eng</language><publisher>Attiki: International Institute of Anticancer Research</publisher><subject>Activating Transcription Factor 3 - biosynthesis ; Activating Transcription Factor 3 - genetics ; Adenocarcinoma - drug therapy ; Antineoplastic Combined Chemotherapy Protocols - pharmacology ; Biological and medical sciences ; Carcinoma, Non-Small-Cell Lung - drug therapy ; Cell Line ; Cell Line, Tumor ; Cisplatin - administration & dosage ; Cisplatin - pharmacology ; Disulfiram - administration & dosage ; Disulfiram - pharmacology ; Drug Synergism ; Female ; Gene Expression Regulation, Neoplastic - drug effects ; Humans ; Lung Neoplasms - drug therapy ; Male ; Medical sciences ; Ovarian Neoplasms - drug therapy ; Prostatic Neoplasms - drug therapy ; Transcription Factor CHOP - biosynthesis ; Transcription Factor CHOP - genetics ; Transcription, Genetic ; Tumors ; Up-Regulation - drug effects</subject><ispartof>Anticancer research, 2012-07, Vol.32 (7), p.2679-2688</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26084359$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22753726$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>O'BRIEN, Anna</creatorcontrib><creatorcontrib>BARBER, Janet E. B</creatorcontrib><creatorcontrib>REID, Stephanie</creatorcontrib><creatorcontrib>NIKNEJAD, Nima</creatorcontrib><creatorcontrib>DIMITROULAKOS, Jim</creatorcontrib><title>Enhancement of Cisplatin Cytotoxicity by Disulfiram Involves Activating Transcription Factor 3</title><title>Anticancer research</title><addtitle>Anticancer Res</addtitle><description>Activating transcription factor 3 (ATF3), a stress-inducible gene, is a regulator of cisplatin-induced cytotoxicity, and enhancement of the ATF3 expression potentiates this cytotoxicity.
ATF3 expression and its binding to the transcription target CHOP were evaluated by western blot and chromatin immunoprecipitation (ChIP), respectively, in a panel of five cell lines (WI38, MCF7, PC3, A549). MTT assays were employed to assess the effects of many drugs, including disulfiram, on cell viability.
ATF3 protein expression was up-regulated after cytotoxic doses of cisplatin treatment and it directly bound to the CHOP gene promoter, increasing this pro-apoptotic protein's expression. In a library screen of 1200 compounds, disulfiram, a dithiocarbamate drug, was identified as an enhancer of the cytotoxic effects of cisplatin. This increased cytotoxic action was synergistic and likely due to their ability to induce ATF3 independently.
Understanding the role of ATF3 in cisplatin-induced cytotoxicity will lead to novel therapeutic approaches that could improve this drug's efficacy.</description><subject>Activating Transcription Factor 3 - biosynthesis</subject><subject>Activating Transcription Factor 3 - genetics</subject><subject>Adenocarcinoma - drug therapy</subject><subject>Antineoplastic Combined Chemotherapy Protocols - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Non-Small-Cell Lung - drug therapy</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>Cisplatin - administration & dosage</subject><subject>Cisplatin - pharmacology</subject><subject>Disulfiram - administration & dosage</subject><subject>Disulfiram - pharmacology</subject><subject>Drug Synergism</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Humans</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Prostatic Neoplasms - drug therapy</subject><subject>Transcription Factor CHOP - biosynthesis</subject><subject>Transcription Factor CHOP - genetics</subject><subject>Transcription, Genetic</subject><subject>Tumors</subject><subject>Up-Regulation - drug effects</subject><issn>0250-7005</issn><issn>1791-7530</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpF0MFLwzAYBfAgipvTf0FyEbwU0nxtuhxH3XQw8DKvljT9qpE2qU1a7H9vxYmnd_nx4L0zsowzGUdZCuycLBlPWZQxli7IlfcfjAkh13BJFpzPIuNiSV639l1ZjS3aQF1Nc-O7RgVjaT4FF9yX0SZMtJzog_FDU5tetXRvR9eM6OlGBzP-6Dd67JX1ujddMM7SndLB9RSuyUWtGo83p1yRl932mD9Fh-fHfb45RB1P4hCBhhLXwDCTyLhOKhBVzRVIFgOyFCusStCcV0zHmokkljUILSosFaAEDity_9vb9e5zQB-K1niNTaMsusEXMePApYQ0nentiQ5li1XR9aZV_VT8fTKDuxNQXqumnodp4_-dYOsEUgnfNwVskA</recordid><startdate>20120701</startdate><enddate>20120701</enddate><creator>O'BRIEN, Anna</creator><creator>BARBER, Janet E. 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B ; REID, Stephanie ; NIKNEJAD, Nima ; DIMITROULAKOS, Jim</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p241t-3c3be830e79e02c4d36df2a39013e05ededb3c22d0c1c06419f36c6deba3e9323</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Activating Transcription Factor 3 - biosynthesis</topic><topic>Activating Transcription Factor 3 - genetics</topic><topic>Adenocarcinoma - drug therapy</topic><topic>Antineoplastic Combined Chemotherapy Protocols - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Non-Small-Cell Lung - drug therapy</topic><topic>Cell Line</topic><topic>Cell Line, Tumor</topic><topic>Cisplatin - administration & dosage</topic><topic>Cisplatin - pharmacology</topic><topic>Disulfiram - administration & dosage</topic><topic>Disulfiram - pharmacology</topic><topic>Drug Synergism</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Humans</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Prostatic Neoplasms - drug therapy</topic><topic>Transcription Factor CHOP - biosynthesis</topic><topic>Transcription Factor CHOP - genetics</topic><topic>Transcription, Genetic</topic><topic>Tumors</topic><topic>Up-Regulation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>O'BRIEN, Anna</creatorcontrib><creatorcontrib>BARBER, Janet E. 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ATF3 expression and its binding to the transcription target CHOP were evaluated by western blot and chromatin immunoprecipitation (ChIP), respectively, in a panel of five cell lines (WI38, MCF7, PC3, A549). MTT assays were employed to assess the effects of many drugs, including disulfiram, on cell viability.
ATF3 protein expression was up-regulated after cytotoxic doses of cisplatin treatment and it directly bound to the CHOP gene promoter, increasing this pro-apoptotic protein's expression. In a library screen of 1200 compounds, disulfiram, a dithiocarbamate drug, was identified as an enhancer of the cytotoxic effects of cisplatin. This increased cytotoxic action was synergistic and likely due to their ability to induce ATF3 independently.
Understanding the role of ATF3 in cisplatin-induced cytotoxicity will lead to novel therapeutic approaches that could improve this drug's efficacy.</abstract><cop>Attiki</cop><pub>International Institute of Anticancer Research</pub><pmid>22753726</pmid><tpages>10</tpages></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Activating Transcription Factor 3 - biosynthesis Activating Transcription Factor 3 - genetics Adenocarcinoma - drug therapy Antineoplastic Combined Chemotherapy Protocols - pharmacology Biological and medical sciences Carcinoma, Non-Small-Cell Lung - drug therapy Cell Line Cell Line, Tumor Cisplatin - administration & dosage Cisplatin - pharmacology Disulfiram - administration & dosage Disulfiram - pharmacology Drug Synergism Female Gene Expression Regulation, Neoplastic - drug effects Humans Lung Neoplasms - drug therapy Male Medical sciences Ovarian Neoplasms - drug therapy Prostatic Neoplasms - drug therapy Transcription Factor CHOP - biosynthesis Transcription Factor CHOP - genetics Transcription, Genetic Tumors Up-Regulation - drug effects |
| title | Enhancement of Cisplatin Cytotoxicity by Disulfiram Involves Activating Transcription Factor 3 |
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