Increased susceptibility of the c-Myc overexpressing cell line, SNU-16, to TNF-alpha.

Abstract:

:Tumor necrosis factor-alpha (TNF-alpha) is a macrophage-derived multifunctional cytokine that acts as a cytostatic or cytotoxic agent in many tumor cells. However, the molecular mechanisms by which tumor cells become sensitive to the cytotoxic action of TNF-alpha are not clear. In this study we demonstrated that the cytotoxicity of TNF-alpha markedly increased in c-Myc overexpressing tumor cells. The stomach cancer cell line, SNU-16, in which c-Myc expression is high due to gene amplification, showed programmed cell death detected by DNA fragmentation and morphological changes. An antisense c-myc S-oligonucleotide specifically inhibited the TNF-alpha-induced apoptosis of SNU-16 cells, provided that the oligonucleotide was added 4 h prior to TNF-alpha treatment. Western immunoblot analysis of p53 and Bax showed that in this cell line, TNF-alpha increased the level of these proteins in a time-dependent manner and that this effect lasted for 12 h. Taken together these data indicate that the deregulation of c-Myc plays an important role in sensitizing tumor cells to TNF-alpha. Furthermore, TNF-alpha-induced apoptosis in the SNU-16 cell line showed increased expression of p53 and Bax protein levels following TNF-alpha treatment. Therefore, we suggest that TNF-alpha-induced apoptosis, which is cytotoxic to tumor cells, is coupled with a p53 and Bax apoptotic pathway.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Park IC,Park MJ,Lee SH,Choe TB,Jang JJ,Hong SI

doi

10.1016/s0304-3835(97)00450-3

subject

Has Abstract

pub_date

1998-03-13 00:00:00

pages

17-23

issue

1-2

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(97)00450-3

journal_volume

125

pub_type

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