Expression of interleukin-8, heme oxygenase-1 and vascular endothelial growth factor in DLD-1 colon carcinoma cells exposed to pyrrolidine dithiocarbamate
Interleukin (IL)-8, heme oxygenase-1 (HO-1), and vascular endothelial growth factor (VEGF) appear to be critically involved in immune responses associated with inflammation, infection and tumor growth. Regulation of these mediators was studied in the human colon carcinoma cell line DLD-1. Here we re...
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Veröffentlicht in: | Carcinogenesis (New York) 2002-08, Vol.23 (8), p.1273-1279 |
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creator | Hellmuth, Markus Wetzler, Christian Nold, Marcel Chang, Jae-Hyung Frank, Stefan Pfeilschifter, Josef Mühl, Heiko |
description | Interleukin (IL)-8, heme oxygenase-1 (HO-1), and vascular endothelial growth factor (VEGF) appear to be critically involved in immune responses associated with inflammation, infection and tumor growth. Regulation of these mediators was studied in the human colon carcinoma cell line DLD-1. Here we report that pyrrolidine dithiocarbamate (PDTC) not only augmented tumor necrosis factor-α-induced release of IL-8, but also mediated IL-8 expression as a single stimulus. Mutational analysis of the IL-8 promotor and electrophoretic mobility shift analysis revealed that activation of the transcription factor activator protein-1 (AP-1) and a constitutive nuclear factor-κB (NF-κB) binding activity in DLD-1 cells were mandatory for PDTC-induced IL-8 expression. Besides IL-8, PDTC also upregulated the expression of HO-1 and VEGF in these cells. Induction of IL-8 by PDTC was not restricted to DLD-1 cells, but was observed in Caco-2 colon carcinoma cells and in peripheral blood mononuclear cells. PDTC is currently advocated for use as a chemotherapeutic drug in the treatment of certain malignancies, among them colorectal cancer. Induction of IL-8, HO-1 and VEGF may affect therapeutic applications of this agent. |
doi_str_mv | 10.1093/carcin/23.8.1273 |
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Regulation of these mediators was studied in the human colon carcinoma cell line DLD-1. Here we report that pyrrolidine dithiocarbamate (PDTC) not only augmented tumor necrosis factor-α-induced release of IL-8, but also mediated IL-8 expression as a single stimulus. Mutational analysis of the IL-8 promotor and electrophoretic mobility shift analysis revealed that activation of the transcription factor activator protein-1 (AP-1) and a constitutive nuclear factor-κB (NF-κB) binding activity in DLD-1 cells were mandatory for PDTC-induced IL-8 expression. Besides IL-8, PDTC also upregulated the expression of HO-1 and VEGF in these cells. Induction of IL-8 by PDTC was not restricted to DLD-1 cells, but was observed in Caco-2 colon carcinoma cells and in peripheral blood mononuclear cells. PDTC is currently advocated for use as a chemotherapeutic drug in the treatment of certain malignancies, among them colorectal cancer. Induction of IL-8, HO-1 and VEGF may affect therapeutic applications of this agent.</description><identifier>ISSN: 0143-3334</identifier><identifier>EISSN: 1460-2180</identifier><identifier>DOI: 10.1093/carcin/23.8.1273</identifier><identifier>PMID: 12151344</identifier><identifier>CODEN: CRNGDP</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>activator protein-1 ; AP-1 ; Biological and medical sciences ; Carcinogenesis, carcinogens and anticarcinogens ; Chemical agents ; Colonic Neoplasms - genetics ; Colonic Neoplasms - pathology ; Electrophoretic Mobility Shift Assay ; EMSA ; Endothelial Growth Factors - genetics ; Enzyme-Linked Immunosorbent Assay ; Gene Expression Regulation, Neoplastic - drug effects ; Heme Oxygenase (Decyclizing) - genetics ; heme oxygenase-1 ; HO-1 ; Humans ; interleukin ; Interleukin-8 - blood ; Interleukin-8 - genetics ; Lymphokines - genetics ; Medical sciences ; Monocytes - metabolism ; NF-κB ; nuclear factor-κB ; PBMC ; PDTC ; peripheral blood mononuclear cells ; pyrrolidine dithiocarbamate ; Pyrrolidines - pharmacology ; Thiocarbamates - pharmacology ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha - physiology ; Tumors ; vascular endothelial growth factor ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; VEGF</subject><ispartof>Carcinogenesis (New York), 2002-08, Vol.23 (8), p.1273-1279</ispartof><rights>2002 INIST-CNRS</rights><rights>Copyright Oxford University Press(England) Aug 2002</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-dd5a7b56bfa20c0b8ea37ffde499528325fb773dce982bcb0244f8cd0a3b678d3</citedby><cites>FETCH-LOGICAL-c463t-dd5a7b56bfa20c0b8ea37ffde499528325fb773dce982bcb0244f8cd0a3b678d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13822958$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12151344$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hellmuth, Markus</creatorcontrib><creatorcontrib>Wetzler, Christian</creatorcontrib><creatorcontrib>Nold, Marcel</creatorcontrib><creatorcontrib>Chang, Jae-Hyung</creatorcontrib><creatorcontrib>Frank, Stefan</creatorcontrib><creatorcontrib>Pfeilschifter, Josef</creatorcontrib><creatorcontrib>Mühl, Heiko</creatorcontrib><title>Expression of interleukin-8, heme oxygenase-1 and vascular endothelial growth factor in DLD-1 colon carcinoma cells exposed to pyrrolidine dithiocarbamate</title><title>Carcinogenesis (New York)</title><addtitle>Carcinogenesis</addtitle><description>Interleukin (IL)-8, heme oxygenase-1 (HO-1), and vascular endothelial growth factor (VEGF) appear to be critically involved in immune responses associated with inflammation, infection and tumor growth. Regulation of these mediators was studied in the human colon carcinoma cell line DLD-1. Here we report that pyrrolidine dithiocarbamate (PDTC) not only augmented tumor necrosis factor-α-induced release of IL-8, but also mediated IL-8 expression as a single stimulus. Mutational analysis of the IL-8 promotor and electrophoretic mobility shift analysis revealed that activation of the transcription factor activator protein-1 (AP-1) and a constitutive nuclear factor-κB (NF-κB) binding activity in DLD-1 cells were mandatory for PDTC-induced IL-8 expression. Besides IL-8, PDTC also upregulated the expression of HO-1 and VEGF in these cells. Induction of IL-8 by PDTC was not restricted to DLD-1 cells, but was observed in Caco-2 colon carcinoma cells and in peripheral blood mononuclear cells. PDTC is currently advocated for use as a chemotherapeutic drug in the treatment of certain malignancies, among them colorectal cancer. Induction of IL-8, HO-1 and VEGF may affect therapeutic applications of this agent.</description><subject>activator protein-1</subject><subject>AP-1</subject><subject>Biological and medical sciences</subject><subject>Carcinogenesis, carcinogens and anticarcinogens</subject><subject>Chemical agents</subject><subject>Colonic Neoplasms - genetics</subject><subject>Colonic Neoplasms - pathology</subject><subject>Electrophoretic Mobility Shift Assay</subject><subject>EMSA</subject><subject>Endothelial Growth Factors - genetics</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Heme Oxygenase (Decyclizing) - genetics</subject><subject>heme oxygenase-1</subject><subject>HO-1</subject><subject>Humans</subject><subject>interleukin</subject><subject>Interleukin-8 - blood</subject><subject>Interleukin-8 - genetics</subject><subject>Lymphokines - genetics</subject><subject>Medical sciences</subject><subject>Monocytes - metabolism</subject><subject>NF-κB</subject><subject>nuclear factor-κB</subject><subject>PBMC</subject><subject>PDTC</subject><subject>peripheral blood mononuclear cells</subject><subject>pyrrolidine dithiocarbamate</subject><subject>Pyrrolidines - pharmacology</subject><subject>Thiocarbamates - pharmacology</subject><subject>Tumor Cells, Cultured</subject><subject>Tumor Necrosis Factor-alpha - physiology</subject><subject>Tumors</subject><subject>vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A</subject><subject>Vascular Endothelial Growth Factors</subject><subject>VEGF</subject><issn>0143-3334</issn><issn>1460-2180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpd0ctu1DAUBmALgehQ2LNCFhKsyNSXXJwl6hSCGIkNSGg2lmOfdNwmdmonMPMqPC0eZUQlVl74O79-nYPQa0rWlNT8SqugrbtifC3WlFX8CVrRvCQZo4I8RStCc55xzvML9CLGO0JoyYv6ObqgjBaU5_kK_bk5jAFitN5h32HrJgg9zPfWZeID3sMA2B-Ot-BUhIxi5Qz-paKeexUwOOOnPfRW9fg2-N_THndKTz6kGLzZbpLXvk_BS00_KKyh7yOGw-gjGDx5PB5D8L011gE2dtpbn3CrBjXBS_SsU32EV-f3Ev34dPP9usm23z5_uf64zXRe8ikzplBVW5RtpxjRpBWgeNV1BvK6LpjgrOjaquJGQy1Yq1vC8rwT2hDF27IShl-i90vuGPzDDHGSg42nosqBn6OkFeGiLsoE3_4H7_wcXOomGa15VQhGEiIL0sHHGKCTY7CDCkdJiTwdTS7bkIxLIU9HSyNvzrlzO4B5HDhfKYF3Z5BWr_ouKKdtfHRcMFYXIrlscTZOcPj3r8K9LKvUTzY_d3Kza5rd16aUO_4XAquzOA</recordid><startdate>20020801</startdate><enddate>20020801</enddate><creator>Hellmuth, Markus</creator><creator>Wetzler, Christian</creator><creator>Nold, Marcel</creator><creator>Chang, Jae-Hyung</creator><creator>Frank, Stefan</creator><creator>Pfeilschifter, Josef</creator><creator>Mühl, Heiko</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>BSCLL</scope><scope>IQODW</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>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20020801</creationdate><title>Expression of interleukin-8, heme oxygenase-1 and vascular endothelial growth factor in DLD-1 colon carcinoma cells exposed to pyrrolidine dithiocarbamate</title><author>Hellmuth, Markus ; Wetzler, Christian ; Nold, Marcel ; Chang, Jae-Hyung ; Frank, Stefan ; Pfeilschifter, Josef ; Mühl, Heiko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c463t-dd5a7b56bfa20c0b8ea37ffde499528325fb773dce982bcb0244f8cd0a3b678d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>activator protein-1</topic><topic>AP-1</topic><topic>Biological and medical sciences</topic><topic>Carcinogenesis, carcinogens and anticarcinogens</topic><topic>Chemical agents</topic><topic>Colonic Neoplasms - genetics</topic><topic>Colonic Neoplasms - pathology</topic><topic>Electrophoretic Mobility Shift Assay</topic><topic>EMSA</topic><topic>Endothelial Growth Factors - genetics</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Heme Oxygenase (Decyclizing) - genetics</topic><topic>heme oxygenase-1</topic><topic>HO-1</topic><topic>Humans</topic><topic>interleukin</topic><topic>Interleukin-8 - blood</topic><topic>Interleukin-8 - genetics</topic><topic>Lymphokines - genetics</topic><topic>Medical sciences</topic><topic>Monocytes - metabolism</topic><topic>NF-κB</topic><topic>nuclear factor-κB</topic><topic>PBMC</topic><topic>PDTC</topic><topic>peripheral blood mononuclear cells</topic><topic>pyrrolidine dithiocarbamate</topic><topic>Pyrrolidines - pharmacology</topic><topic>Thiocarbamates - pharmacology</topic><topic>Tumor Cells, Cultured</topic><topic>Tumor Necrosis Factor-alpha - physiology</topic><topic>Tumors</topic><topic>vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A</topic><topic>Vascular Endothelial Growth Factors</topic><topic>VEGF</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hellmuth, Markus</creatorcontrib><creatorcontrib>Wetzler, Christian</creatorcontrib><creatorcontrib>Nold, Marcel</creatorcontrib><creatorcontrib>Chang, Jae-Hyung</creatorcontrib><creatorcontrib>Frank, Stefan</creatorcontrib><creatorcontrib>Pfeilschifter, Josef</creatorcontrib><creatorcontrib>Mühl, Heiko</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Carcinogenesis (New York)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hellmuth, Markus</au><au>Wetzler, Christian</au><au>Nold, Marcel</au><au>Chang, Jae-Hyung</au><au>Frank, Stefan</au><au>Pfeilschifter, Josef</au><au>Mühl, Heiko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of interleukin-8, heme oxygenase-1 and vascular endothelial growth factor in DLD-1 colon carcinoma cells exposed to pyrrolidine dithiocarbamate</atitle><jtitle>Carcinogenesis (New York)</jtitle><addtitle>Carcinogenesis</addtitle><date>2002-08-01</date><risdate>2002</risdate><volume>23</volume><issue>8</issue><spage>1273</spage><epage>1279</epage><pages>1273-1279</pages><issn>0143-3334</issn><eissn>1460-2180</eissn><coden>CRNGDP</coden><abstract>Interleukin (IL)-8, heme oxygenase-1 (HO-1), and vascular endothelial growth factor (VEGF) appear to be critically involved in immune responses associated with inflammation, infection and tumor growth. Regulation of these mediators was studied in the human colon carcinoma cell line DLD-1. Here we report that pyrrolidine dithiocarbamate (PDTC) not only augmented tumor necrosis factor-α-induced release of IL-8, but also mediated IL-8 expression as a single stimulus. Mutational analysis of the IL-8 promotor and electrophoretic mobility shift analysis revealed that activation of the transcription factor activator protein-1 (AP-1) and a constitutive nuclear factor-κB (NF-κB) binding activity in DLD-1 cells were mandatory for PDTC-induced IL-8 expression. Besides IL-8, PDTC also upregulated the expression of HO-1 and VEGF in these cells. Induction of IL-8 by PDTC was not restricted to DLD-1 cells, but was observed in Caco-2 colon carcinoma cells and in peripheral blood mononuclear cells. PDTC is currently advocated for use as a chemotherapeutic drug in the treatment of certain malignancies, among them colorectal cancer. Induction of IL-8, HO-1 and VEGF may affect therapeutic applications of this agent.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>12151344</pmid><doi>10.1093/carcin/23.8.1273</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
subjects | activator protein-1 AP-1 Biological and medical sciences Carcinogenesis, carcinogens and anticarcinogens Chemical agents Colonic Neoplasms - genetics Colonic Neoplasms - pathology Electrophoretic Mobility Shift Assay EMSA Endothelial Growth Factors - genetics Enzyme-Linked Immunosorbent Assay Gene Expression Regulation, Neoplastic - drug effects Heme Oxygenase (Decyclizing) - genetics heme oxygenase-1 HO-1 Humans interleukin Interleukin-8 - blood Interleukin-8 - genetics Lymphokines - genetics Medical sciences Monocytes - metabolism NF-κB nuclear factor-κB PBMC PDTC peripheral blood mononuclear cells pyrrolidine dithiocarbamate Pyrrolidines - pharmacology Thiocarbamates - pharmacology Tumor Cells, Cultured Tumor Necrosis Factor-alpha - physiology Tumors vascular endothelial growth factor Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors VEGF |
title | Expression of interleukin-8, heme oxygenase-1 and vascular endothelial growth factor in DLD-1 colon carcinoma cells exposed to pyrrolidine dithiocarbamate |
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