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5-Fluorouracil induces apoptosis through the suppression of NF-kappaB activity in human salivary gland cancer cells.

Abstract：

:Activation of the transcription factor NF-kappaB results in protection against apoptosis, and the chemotherapeutic agent 5-Fluorouracil (5-FU) exerts its cytotoxic effect through the induction of apoptosis. Thus, we examined whether 5-FU could induce apoptosis through the suppression of NF-kappaB activity. We found that upon treatment of a human salivary gland cancer cell line (cl-1) with 5-FU, the NF-kappaB activity was suppressed in a time-dependent manner. This inhibition was mediated by a prevention of the degradation of the inhibitory IkappaB-alpha protein. In addition, the expression of TRAF-2 and cIAP-1, which are transcriptionally regulated by NF-kappaB and function as anti-apoptotic molecules through the interruption of caspase pathway, was also inhibited by 5-FU. Finally, the activity of caspase-8 and caspase-3 showed a significant increase in response to 5-FU. By flow cytometric analysis, 5-FU did not affect the expression level of Fas on the cell surface. Thus, our results suggest that one of the molecular mechanisms involved in 5-FU-induced apoptosis in cl-1 cells may be due to the suppression of NF-kappaB activity, resulting in the activation of the pro-apoptotic pathway.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Aota K,Azuma M,Yamashita T,Tamatani T,Motegi K,Ishimaru N,Hayashi Y,Sato M

doi

10.1006/bbrc.2000.3072

subject

Has Abstract

pub_date

2000-07-14 00:00:00

pages

1168-74

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(00)93072-9

journal_volume

273

pub_type

杂志文章

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