5-Fluorouracil inhibits nitric oxide production through the inactivation of IκB kinase in stomach cancer cells

In Duk Jung, So Young Yang, Chang Gyo Park, Kyung Bok Lee, Jong Seung Kim, Seok Yong Lee, Jeung Whan Han, Hyang Woo Lee, Hoi Young Lee

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11 Citations (Scopus)

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 languageEnglish
Pages (from-to)1439-1445
Number of pages7
JournalBiochemical Pharmacology
Volume64
Issue number10
DOIs
Publication statusPublished - 2002 Nov 15

Keywords

  • 5-Fluorouracil
  • IκBα
  • NF-κB
  • Nitric oxide
  • Stomach cancer

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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  • Cite this

    Jung, I. D., Yang, S. Y., Park, C. G., Lee, K. B., Kim, J. S., Lee, S. Y., Han, J. W., Lee, H. W., & Lee, H. Y. (2002). 5-Fluorouracil inhibits nitric oxide production through the inactivation of IκB kinase in stomach cancer cells. Biochemical Pharmacology, 64(10), 1439-1445. https://doi.org/10.1016/S0006-2952(02)01381-3