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)