Sulfasalazine down-regulates the expression of the angiogenic factors platelet-derived endothelial cell growth factor/thymidine phosphorylase and interleukin-8 in human monocytic-macrophage THP1 and U937 cells

Michiel de Bruin, Godefridus J Peters, Ruud Oerlemans, Yehuda G Assaraf, Allan J Masterson, Auke D Adema, Ben A C Dijkmans, Herbert M Pinedo, Gerrit Jansen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) and interleukin-8 (IL-8) are angiogenic factors produced by tumor infiltrating macrophages. Here, we show that prolonged exposure of human monocytic/macrophage THP1 and U937 cells to sulfasalazine, an anti-inflammatory drug and inhibitor of nuclear factor-kappaB (NF-kappaB), resulted in down-regulation of PD-ECGF/TP and IL-8 (mRNA, protein and activity) along with elimination of their induction by tumor necrosis factor-alpha and interferon-gamma. Concomitantly, sulfasalazine-exposed cells were markedly resistant to 5'-deoxyfluorouridine, the last intermediate of capecitabine requiring activation by PD-ECGF/TP. This is the first report suggesting that disruption of NF-kappaB-dependent signaling pathways can provoke a marked and sustained down-regulation of macrophage-related angiogenic factors. However, this may also negatively affect capecitabine efficacy.

Original languageEnglish
Pages (from-to)1054-60
Number of pages7
JournalMolecular Pharmacology
Volume66
Issue number4
DOIs
Publication statusPublished - Oct 2004

Cite this

@article{16f6b30c642b4c1ca52f038961251476,
title = "Sulfasalazine down-regulates the expression of the angiogenic factors platelet-derived endothelial cell growth factor/thymidine phosphorylase and interleukin-8 in human monocytic-macrophage THP1 and U937 cells",
abstract = "Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) and interleukin-8 (IL-8) are angiogenic factors produced by tumor infiltrating macrophages. Here, we show that prolonged exposure of human monocytic/macrophage THP1 and U937 cells to sulfasalazine, an anti-inflammatory drug and inhibitor of nuclear factor-kappaB (NF-kappaB), resulted in down-regulation of PD-ECGF/TP and IL-8 (mRNA, protein and activity) along with elimination of their induction by tumor necrosis factor-alpha and interferon-gamma. Concomitantly, sulfasalazine-exposed cells were markedly resistant to 5'-deoxyfluorouridine, the last intermediate of capecitabine requiring activation by PD-ECGF/TP. This is the first report suggesting that disruption of NF-kappaB-dependent signaling pathways can provoke a marked and sustained down-regulation of macrophage-related angiogenic factors. However, this may also negatively affect capecitabine efficacy.",
keywords = "Angiogenesis Inducing Agents/metabolism, Anti-Inflammatory Agents, Non-Steroidal/pharmacology, Blotting, Western, Gene Expression/drug effects, Humans, Interleukin-8/genetics, Macrophages/drug effects, Monocytes/cytology, NF-kappa B/metabolism, NF-kappa B p50 Subunit, RNA, Messenger/metabolism, Receptors, Interferon/metabolism, Receptors, Tumor Necrosis Factor, Type I/metabolism, Receptors, Tumor Necrosis Factor, Type II/metabolism, Sulfasalazine/pharmacology, Thymidine Phosphorylase/genetics, Transcription Factor RelA, Transcription Factors/metabolism, U937 Cells",
author = "{de Bruin}, Michiel and Peters, {Godefridus J} and Ruud Oerlemans and Assaraf, {Yehuda G} and Masterson, {Allan J} and Adema, {Auke D} and Dijkmans, {Ben A C} and Pinedo, {Herbert M} and Gerrit Jansen",
year = "2004",
month = "10",
doi = "10.1124/mol.104.000315",
language = "English",
volume = "66",
pages = "1054--60",
journal = "Molecular Pharmacology",
issn = "0026-895X",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "4",

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Sulfasalazine down-regulates the expression of the angiogenic factors platelet-derived endothelial cell growth factor/thymidine phosphorylase and interleukin-8 in human monocytic-macrophage THP1 and U937 cells. / de Bruin, Michiel; Peters, Godefridus J; Oerlemans, Ruud; Assaraf, Yehuda G; Masterson, Allan J; Adema, Auke D; Dijkmans, Ben A C; Pinedo, Herbert M; Jansen, Gerrit.

In: Molecular Pharmacology, Vol. 66, No. 4, 10.2004, p. 1054-60.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Sulfasalazine down-regulates the expression of the angiogenic factors platelet-derived endothelial cell growth factor/thymidine phosphorylase and interleukin-8 in human monocytic-macrophage THP1 and U937 cells

AU - de Bruin, Michiel

AU - Peters, Godefridus J

AU - Oerlemans, Ruud

AU - Assaraf, Yehuda G

AU - Masterson, Allan J

AU - Adema, Auke D

AU - Dijkmans, Ben A C

AU - Pinedo, Herbert M

AU - Jansen, Gerrit

PY - 2004/10

Y1 - 2004/10

N2 - Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) and interleukin-8 (IL-8) are angiogenic factors produced by tumor infiltrating macrophages. Here, we show that prolonged exposure of human monocytic/macrophage THP1 and U937 cells to sulfasalazine, an anti-inflammatory drug and inhibitor of nuclear factor-kappaB (NF-kappaB), resulted in down-regulation of PD-ECGF/TP and IL-8 (mRNA, protein and activity) along with elimination of their induction by tumor necrosis factor-alpha and interferon-gamma. Concomitantly, sulfasalazine-exposed cells were markedly resistant to 5'-deoxyfluorouridine, the last intermediate of capecitabine requiring activation by PD-ECGF/TP. This is the first report suggesting that disruption of NF-kappaB-dependent signaling pathways can provoke a marked and sustained down-regulation of macrophage-related angiogenic factors. However, this may also negatively affect capecitabine efficacy.

AB - Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) and interleukin-8 (IL-8) are angiogenic factors produced by tumor infiltrating macrophages. Here, we show that prolonged exposure of human monocytic/macrophage THP1 and U937 cells to sulfasalazine, an anti-inflammatory drug and inhibitor of nuclear factor-kappaB (NF-kappaB), resulted in down-regulation of PD-ECGF/TP and IL-8 (mRNA, protein and activity) along with elimination of their induction by tumor necrosis factor-alpha and interferon-gamma. Concomitantly, sulfasalazine-exposed cells were markedly resistant to 5'-deoxyfluorouridine, the last intermediate of capecitabine requiring activation by PD-ECGF/TP. This is the first report suggesting that disruption of NF-kappaB-dependent signaling pathways can provoke a marked and sustained down-regulation of macrophage-related angiogenic factors. However, this may also negatively affect capecitabine efficacy.

KW - Angiogenesis Inducing Agents/metabolism

KW - Anti-Inflammatory Agents, Non-Steroidal/pharmacology

KW - Blotting, Western

KW - Gene Expression/drug effects

KW - Humans

KW - Interleukin-8/genetics

KW - Macrophages/drug effects

KW - Monocytes/cytology

KW - NF-kappa B/metabolism

KW - NF-kappa B p50 Subunit

KW - RNA, Messenger/metabolism

KW - Receptors, Interferon/metabolism

KW - Receptors, Tumor Necrosis Factor, Type I/metabolism

KW - Receptors, Tumor Necrosis Factor, Type II/metabolism

KW - Sulfasalazine/pharmacology

KW - Thymidine Phosphorylase/genetics

KW - Transcription Factor RelA

KW - Transcription Factors/metabolism

KW - U937 Cells

U2 - 10.1124/mol.104.000315

DO - 10.1124/mol.104.000315

M3 - Article

VL - 66

SP - 1054

EP - 1060

JO - Molecular Pharmacology

JF - Molecular Pharmacology

SN - 0026-895X

IS - 4

ER -