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

doi:10.1016/S0006-2952(02)01381-3

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

Research output: Contribution to journal › Article › peer-review

12 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 language	English
Pages (from-to)	1439-1445
Number of pages	7
Journal	Biochemical Pharmacology
Volume	64
Issue number	10
DOIs	https://doi.org/10.1016/S0006-2952(02)01381-3
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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/S0006-2952(02)01381-3

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5-Fluorouracil inhibits nitric oxide production through the inactivation of IκB kinase in stomach cancer cells. / Jung, In Duk; Yang, So Young; Park, Chang Gyo; Lee, Kyung Bok; Kim, Jong Seung; Lee, Seok Yong; Han, Jeung Whan; Lee, Hyang Woo; Lee, Hoi Young.

In: Biochemical Pharmacology, Vol. 64, No. 10, 15.11.2002, p. 1439-1445.

Research output: Contribution to journal › Article › peer-review

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title = "5-Fluorouracil inhibits nitric oxide production through the inactivation of IκB 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)-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.",

keywords = "5-Fluorouracil, IκBα, NF-κB, Nitric oxide, Stomach cancer",

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

note = "Funding Information: This work was supported by the Korea Science and Engineering Foundation (KOSEF) through the Cancer Metastasis Research Center (CMRC) at Yonsei University. ",

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AU - Jung, In Duk

AU - Yang, So Young

AU - Park, Chang Gyo

AU - Lee, Kyung Bok

AU - Kim, Jong Seung

AU - Lee, Seok Yong

AU - Han, Jeung Whan

AU - Lee, Hyang Woo

AU - Lee, Hoi Young

N1 - Funding Information: This work was supported by the Korea Science and Engineering Foundation (KOSEF) through the Cancer Metastasis Research Center (CMRC) at Yonsei University.

PY - 2002/11/15

Y1 - 2002/11/15

N2 - 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.

AB - 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.

KW - 5-Fluorouracil

KW - IκBα

KW - NF-κB

KW - Nitric oxide

KW - Stomach cancer

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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