論文 - 詳細
| RRC ID | 44764 |
|---|---|
| 著者 | Suzuki K, Sakaguchi M, Tanaka S, Yoshimoto T, Takaoka M. |
| タイトル | Prolyl oligopeptidase inhibition-induced growth arrest of human gastric cancer cells. |
| ジャーナル | Biochem Biophys Res Commun |
| Abstract |
Prolyl oligopeptidase (POP) is a serine endopeptidase that hydrolyzes post-proline peptide bonds in peptides that are <30 amino acids in length. We recently reported that POP inhibition suppressed the growth of human neuroblastoma cells. The growth suppression was associated with pronounced G0/G1 cell cycle arrest and increased levels of the CDK inhibitor p27(kip1) and the tumor suppressor p53. In this study, we investigated the mechanism of POP inhibition-induced cell growth arrest using a human gastric cancer cell line, KATO III cells, which had a p53 gene deletion. POP specific inhibitors, 3-({4-[2-(E)-styrylphenoxy]butanoyl}-l-4-hydroxyprolyl)-thiazolidine (SUAM-14746) and benzyloxycarbonyl-thioprolyl-thioprolinal, or RNAi-mediated POP knockdown inhibited the growth of KATO III cells irrespective of their p53 status. SUAM-14746-induced growth inhibition was associated with G0/G1 cell cycle phase arrest and increased levels of p27(kip1) in the nuclei and the pRb2/p130 protein expression. Moreover, SUAM-14746-mediated cell cycle arrest of KATO III cells was associated with an increase in the quiescent G0 state, defined by low level staining for the proliferation marker, Ki-67. These results indicate that POP may be a positive regulator of cell cycle progression by regulating the exit from and/or reentry into the cell cycle by KATO III cells. |
| 巻・号 | 443(1) |
| ページ | 91-6 |
| 公開日 | 2014-1-3 |
| DOI | 10.1016/j.bbrc.2013.11.051 |
| PII | S0006-291X(13)01944-X |
| PMID | 24269815 |
| MeSH | Cell Cycle Checkpoints* / drug effects Cell Cycle Checkpoints* / genetics Cell Line, Tumor Cell Nucleus / metabolism Cell Proliferation / drug effects Cyclin-Dependent Kinase Inhibitor p27 / metabolism Gene Deletion Gene Knockdown Techniques Humans Proline / analogs & derivatives Proline / pharmacology Prolyl Oligopeptidases RNA Interference Serine Endopeptidases / genetics Serine Endopeptidases / metabolism* Stomach Neoplasms / enzymology* Stomach Neoplasms / pathology* Thiazolidines / pharmacology |
| IF | 2.985 |
| 引用数 | 12 |
| WOS 分野 | BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | T98G(RCB1954) |