%0 Journal Article %A Michiel de Bruin %A Godefridus J. Peters %A Ruud Oerlemans %A Yehuda G. Assaraf %A Allan J. Masterson %A Auke D. Adema %A Ben A. C. Dijkmans %A Herbert M. Pinedo %A Gerrit Jansen %T 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 %D 2004 %R 10.1124/mol.104.000315 %J Molecular Pharmacology %P 1054-1060 %V 66 %N 4 %X 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-κB (NF-κB), 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-α and interferon-γ. 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-κB-dependent signaling pathways can provoke a marked and sustained down-regulation of macrophage-related angiogenic factors. However, this may also negatively affect capecitabine efficacy. %U https://molpharm.aspetjournals.org/content/molpharm/66/4/1054.full.pdf