RRC ID 42656
Author Islam S, Hassan F, Tumurkhuu G, Ito H, Koide N, Mori I, Yoshida T, Yokochi T.
Title 5-Fluorouracil prevents lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophage cells by inhibiting Akt-dependent nuclear factor-kappaB activation.
Journal Cancer Chemother Pharmacol
Abstract 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)-kappaB and the subsequent nuclear translocation. Furthermore, 5-FU inhibited the phosphorylation of Akt, an upstream molecule of NF-kappaB 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-kappaB activation.
Volume 59(2)
Pages 227-33
Published 2007-2-1
DOI 10.1007/s00280-006-0261-2
PMID 16724238
MeSH Active Transport, Cell Nucleus / drug effects Animals Antimetabolites, Antineoplastic / pharmacology Cell Line Cell Nucleus / drug effects Cell Nucleus / metabolism Cell Survival / drug effects Dose-Response Relationship, Drug Fluorouracil / pharmacology* Lipopolysaccharides / pharmacology* Luciferases / genetics Luciferases / metabolism Macrophages / cytology Macrophages / drug effects* Macrophages / metabolism Mitogen-Activated Protein Kinases / metabolism NF-kappa B / antagonists & inhibitors* NF-kappa B / metabolism Nitric Oxide / biosynthesis* Nitric Oxide Synthase Type II / antagonists & inhibitors Nitric Oxide Synthase Type II / genetics Nitric Oxide Synthase Type II / metabolism Proto-Oncogene Proteins c-akt / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction Time Factors
IF 2.967
Times Cited 10
WOS Category PHARMACOLOGY & PHARMACY ONCOLOGY
Resource
Human and Animal Cells