title: Antiangiogenic effect of a selective 5-HT4 receptor agonist.
abstract: BACKGROUND
  Serotonin (5-hydroxytryptamine, 5-HT) is reported to regulate cell growth in a wide variety of cell types in different carcinomas. 5-HT exerts complex actions on blood vessels, dependent on its interactions with a multiplicity of 5-HT receptors. In the present study, we aimed to investigate the potential antiangiogenic effect of mosapride citrate, a selective 5-HT4 receptor agonist, known to have prokinetic properties on the gastrointestinal tract. For this purpose, cultured human umbilical vein endothelial cells (HUVECs) were used as an in vitro model.
  
  
  METHODS
  The effect of mosapride citrate on the proliferative activity of HUVECs was assessed by the MTS assay. Then, the apoptosis and the cell cycle detection assays were performed. The effect of mosapride citrate on the ability of HUVECs to adhere and migrate on extracellular matrix proteins (ECMs), as well as their ability to form vascular-like structures on Matrigel was investigated.
  
  
  RESULTS
  Mosapride citrate inhibited the proliferative activity of HUVECs, dependent on cell cycle arrest, and not on apoptosis. A dose-dependent increase in the percentage of cells in the G0/G1 phase of the cell cycle in mosapride-treated HUVECs was observed. Mosapride citrate also significantly inhibited the ability of HUVECs to migrate, but not to adhere on ECMs. Additionally, mosapride citrate dose-dependently inhibited the tube-like formation ability of HUVECs on matrigel, an important event in the process of angiogenesis.
  
  
  CONCLUSIONS
  The present results demonstrate the antiangiogenic activity of mosapride citrate in vitro and the possibility of its application as a new anti-cancer agent is suggested.
authors.affiliation: Department of Surgical Oncology, University of Tokyo, Tokyo, Japan. takn-tky@umin.ac.jp <takn-tky@umin.ac.jp>
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Nelson H
authors.initials: NH
authors.lastname: Tsuno
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Shuno
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Sasaki
authors.forename: Kumiko
authors.initials: K
authors.lastname: Hongo
authors.forename: Yurai
authors.initials: Y
authors.lastname: Okaji
authors.forename: Eiji
authors.initials: E
authors.lastname: Sunami
authors.forename: Joji
authors.initials: J
authors.lastname: Kitayama
authors.forename: Koki
authors.initials: K
authors.lastname: Takahashi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nagawa
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D008958:Models, Molecular; D009025:Morpholines / Q000737:chemistry / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D044422:Receptors, Serotonin, 5-HT4 / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D001549:Benzamides; D009025:Morpholines; D017366:Serotonin Receptor Agonists; D044422:Receptors, Serotonin, 5-HT4; C062720:mosapride