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 JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1054 LP - 1060 DO - 10.1124/mol.104.000315 VL - 66 IS - 4 AU - Michiel de Bruin AU - Godefridus J. Peters AU - Ruud Oerlemans AU - Yehuda G. Assaraf AU - Allan J. Masterson AU - Auke D. Adema AU - Ben A. C. Dijkmans AU - Herbert M. Pinedo AU - Gerrit Jansen Y1 - 2004/10/01 UR - http://molpharm.aspetjournals.org/content/66/4/1054.abstract 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-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. ER -