title: 5-Fluorouracil inhibits nitric oxide production through the inactivation of IkappaB kinase in stomach cancer cells.
abstract: The antimetabolite 5-fluorouracil (5-FU) is one of the more prominent clinical antitumor agents available for the treatment of stomach and colorectal cancers. In the present study, we characterized the effects of 5-FU on nitric oxide (NO) production by cells from the stomach cancer cell line NCI-N87. A cytokine mixture [interleukin (IL)-1beta/interferon (IFN)-gamma] increased the production of NO by stomach cancer cells in a concentration- and time-dependent manner. Pretreatment with 5-FU inhibited the production of NO that was stimulated by the cytokine mixture and reduced the expression of iNOS. The cytokine mixture activated nuclear factor kappaB (NF-kappaB) in a concentration- and time-dependent manner, which was blocked by 5-FU pretreatment. The pretreatment with 5-FU stabilized IkappaBalpha and inactivated IkappaB kinase. Collectively, these data suggest that the efficacy of 5-FU may include the inactivation of IkappaB kinase and the inhibition of NO production.
authors.affiliation: College of Medicine, Konyang University, Nonsan 320-711, South Korea.
authors.forename: In Duk
authors.initials: ID
authors.lastname: Jung
authors.forename: So Young
authors.initials: SY
authors.lastname: Yang
authors.forename: Chang Gyo
authors.initials: CG
authors.lastname: Park
authors.forename: Kyung Bok
authors.initials: KB
authors.lastname: Lee
authors.forename: Jong Seung
authors.initials: JS
authors.lastname: Kim
authors.forename: Seok Yong
authors.initials: SY
authors.lastname: Lee
authors.forename: Jeung Whan
authors.initials: JW
authors.lastname: Han
authors.forename: Hyang Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Hoi Young
authors.initials: HY
authors.lastname: Lee
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D000964:Antimetabolites, Antineoplastic; D016207:Cytokines; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; D005472:Fluorouracil