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Published on: March 30, 2019
Antiangiogenic effect of a selective 5-HT4 receptor agonist
Takeshi Nishikawa1, Nelson H Tsuno, Yasutaka Shuno
1Department of Surgical Oncology, University of Tokyo, Tokyo, Japan. takn-tky@umin.ac.jp <takn-tky@umin.ac.jp>
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.
Material And 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.
Conclusion:
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.
Insights
Mosapride citrate, a serotonin (5-HT4) agonist, demonstrated anti-angiogenic effects by inhibiting endothelial cell proliferation and migration. This suggests its potential as a novel anti-cancer therapeutic agent.
Area of Science:
- Biomedical research
- Pharmacology
- Cancer biology
Background:
- Serotonin (5-hydroxytryptamine, 5-HT) influences cell growth in various carcinomas.
- 5-HT has complex effects on blood vessels via multiple 5-HT receptors.
- Mosapride citrate is a selective 5-HT4 receptor agonist with known prokinetic properties.
Purpose of the Study:
- To investigate the anti-angiogenic potential of mosapride citrate.
- To evaluate mosapride citrate's effects on human umbilical vein endothelial cells (HUVECs) in vitro.
Main Methods:
- Assessed HUVEC proliferation using MTS assay.
- Performed apoptosis and cell cycle detection assays.
- Investigated HUVEC adhesion, migration, and tube formation on Matrigel.
Main Results:
- Mosapride citrate inhibited HUVEC proliferation via cell cycle arrest (G0/G1 phase), not apoptosis.
- Significantly reduced HUVEC migration and tube-like structure formation.
- Did not affect HUVEC adhesion to extracellular matrix proteins.
Conclusions:
- Mosapride citrate exhibits in vitro anti-angiogenic activity.
- Suggests potential application of mosapride citrate as a novel anti-cancer agent.
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