title: Prolyl oligopeptidase participates in cell cycle progression in a human neuroblastoma cell line.
abstract: Prolyl oligopeptidase (POP) is a post-proline cleaving enzyme, which is widely distributed in various organs, with high levels in the brain. In this study, we investigated the effects of a selective POP inhibitor, 3-({4-[2-(E)-styrylphenoxy]butanoyl}-l-4-hydroxyprolyl)-thiazolidine (SUAM-14746), on the growth of NB-1 human neuroblastoma cells. SUAM-14746 treatment for 24-72 h suppresses the growth of NB-1 cells without cell death in a dose-dependent manner (10-60 μM). Similar suppressive effects were observed with another POP inhibitor benzyloxycarbonyl-thioprolyl-thioprolinal. The SUAM-14746-induced growth inhibition in NB-1 cells was associated with pronounced G(0)/G(1) arrest and reduced levels of phosphorylated retinoblastoma protein (pRb), cyclin E, and cyclin dependent kinase (CDK) 2, and increased levels of the CDK inhibitor p27(kip1) and the tumor suppressor p53. SUAM-14746 also induced transient inhibition of S and G(2)/M phase progression, which was correlated with retardation of the decrease in the levels of cyclins A and B. Moreover, RNAi-mediated knockdown of POP also led to inhibition of NB-1 cell growth and the effect was accompanied by G(0)/G(1) arrest. These results indicate that POP is a part of the machinery that controls the cell cycle.
authors.affiliation: Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki Osaka, 569-1094, Japan. sakaguti@gly.oups.ac.jp
authors.forename: Minoru
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuda
authors.forename: Eiko
authors.initials: E
authors.lastname: Matsumura
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Masanori
authors.initials: M
authors.lastname: Takaoka
mesh_terms: D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D011392:Proline / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000085822:Prolyl Oligopeptidases; D034741:RNA, Small Interfering / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics / Q000502:physiology*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D053778:Thiazolidines / Q000493:pharmacokinetics*
chemical_list: C560755:3-((4-(2-styrylphenoxy)butanoyl)-4-hydroxyprolyl)thiazolidine; D034741:RNA, Small Interfering; D015842:Serine Proteinase Inhibitors; D053778:Thiazolidines; D011392:Proline; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases