| 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
|
| リソース情報 |
| ヒト・動物細胞 |
T98G(RCB1954) |
