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)-1β/interferon (IFN)-γ] 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 κB (NF-κB) in a concentration- and time-dependent manner, which was blocked by 5-FU pretreatment. The pretreatment with 5-FU stabilized IκBα and inactivated IκB kinase. Collectively, these data suggest that the efficacy of 5-FU may include the inactivation of IκB kinase and the inhibition of NO production.
Original language | English |
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Pages (from-to) | 1439-1445 |
Number of pages | 7 |
Journal | Biochemical Pharmacology |
Volume | 64 |
Issue number | 10 |
DOIs | |
Publication status | Published - 2002 Nov 15 |
Externally published | Yes |
Keywords
- 5-Fluorouracil
- IκBα
- NF-κB
- Nitric oxide
- Stomach cancer
ASJC Scopus subject areas
- Biochemistry
- Pharmacology