Journal
CANCER CHEMOTHERAPY AND PHARMACOLOGY
Volume 59, Issue 2, Pages 227-233Publisher
SPRINGER
DOI: 10.1007/s00280-006-0261-2
Keywords
5-FU; LPS; NO; Akt; NF-kappa B; iNOS
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The effect of 5-fluorouracil (5-FU) on the production of nitric oxide ( NO) in macrophages was examined by using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. 5-FU at non-toxic concentrations significantly inhibited NO production in LPS-stimulated RAW 264.7 cells. The inhibition by 5-FU was mediated by attenuated expression of an inducible NO synthase protein and mRNA. 5-FU inhibited the activation of nuclear factor (NF)-kB and the subsequent nuclear translocation. Furthermore, 5-FU inhibited the phosphorylation of Akt, an upstream molecule of NF-kB signaling. 5-FU did not affect a series of mitogen-activated protein kinases. Therefore, 5-FU was suggested to inhibit the LPS-induced NO production in activated macrophages through preventing Akt-dependent NF-kB activation.
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