Antiangiogenic effect of a selective 5-HT4 receptor agonist.
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.
Nishikawa
Takeshi
T
Department of Surgical Oncology, University of Tokyo, Tokyo, Japan. takn-tky@umin.ac.jp <takn-tky@umin.ac.jp>
Tsuno
Nelson H
NH
Shuno
Yasutaka
Y
Sasaki
Kazuhito
K
Hongo
Kumiko
K
Okaji
Yurai
Y
Sunami
Eiji
E
Kitayama
Joji
J
Takahashi
Koki
K
Nagawa
Hirokazu
H
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
D020533:Angiogenesis Inhibitors; D001549:Benzamides; D009025:Morpholines; D017366:Serotonin Receptor Agonists; D044422:Receptors, Serotonin, 5-HT4; C062720:mosapride