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
Hauptverfasser: Hellmuth, Markus, Wetzler, Christian, Nold, Marcel, Chang, Jae-Hyung, Frank, Stefan, Pfeilschifter, Josef, Mühl, Heiko
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container_issue 8
container_start_page 1273
container_title Carcinogenesis (New York)
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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. 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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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