Journal Article

Expression of interleukin-8, heme oxygenase-1 and vascular endothelial growth factor in DLD-1 colon carcinoma cells exposed to pyrrolidine dithiocarbamate

Markus Hellmuth, Christian Wetzler, Marcel Nold, Jae-Hyung Chang, Stefan Frank, Josef Pfeilschifter and Heiko Mühl

in Carcinogenesis

Volume 23, issue 8, pages 1273-1279
Published in print August 2002 | ISSN: 0143-3334
Published online August 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.8.1273
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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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.

Keywords: AP-1, activator protein-1; EMSA, electrophoretic mobility shift assay; HO-1, heme oxygenase-1; IL, interleukin; NF-κB, nuclear factor-κB; PBMC, peripheral blood mononuclear cells; PDTC, pyrrolidine dithiocarbamate; VEGF, vascular endothelial growth factor

Journal Article.  5389 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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