RRC ID |
41855
|
著者 |
Ueda M, Kokura S, Imamoto E, Naito Y, Handa O, Takagi T, Yoshida N, Yoshikawa T.
|
タイトル |
Blocking of NF-kappaB activation enhances the tumor necrosis factor alpha-induced apoptosis of a human gastric cancer cell line.
|
ジャーナル |
Cancer Lett
|
Abstract |
The transcription factor NF-kappaB is constitutively activated in many human cancers and induces the expression of multiple genes, including those of anti-apoptotic proteins. This study investigated the mechanism by which human gastric cancer cells (MKN45) are resistant to apoptosis induced by tumor necrosis factor alpha (TNF-alpha). Confluent monolayers of MKN45 cells were either pretreated or not for 60 min with PSI, a peptide aldehyde known to specifically inhibit the chymotrypsin-like activity of 26S proteasome. Cells were subsequently stimulated with recombinant human TNF-alpha, and cell viabilities were determined by the WST-1 assay. Apoptosis was confirmed by fluorescence microscopy after staining with Hoechst 33342, and DNA fragmentation was determined by a DNA fragmentation detection kit. A 24-h incubation with either TNF-alpha or PSI alone did not affect cell viabilities; however, pretreatment with PSI significantly enhanced the level of apoptosis induced by TNF-alpha. Therefore, this study suggests the possibility that blocking of NF-kappaB activity renders gastric cancer cells susceptible to the apoptosis induced by TNF-alpha.
|
巻・号 |
193(2)
|
ページ |
177-82
|
公開日 |
2003-4-25
|
DOI |
10.1016/s0304-3835(03)00002-8
|
PII |
S0304383503000028
|
PMID |
12706875
|
MeSH |
Apoptosis*
Cell Survival
Cysteine Endopeptidases / metabolism
DNA Fragmentation
Dose-Response Relationship, Drug
Humans
Microscopy, Fluorescence
Multienzyme Complexes / metabolism
NF-kappa B / antagonists & inhibitors*
NF-kappa B / metabolism*
Proteasome Endopeptidase Complex
Recombinant Proteins / pharmacology
Stomach Neoplasms / metabolism*
Time Factors
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha / metabolism*
Ubiquitin / metabolism
|
IF |
7.36
|
引用数 |
13
|
WOS 分野
|
ONCOLOGY
|
リソース情報 |
ヒト・動物細胞 |
MKN45(RCB1001) |