title: Y25130 hydrochloride, a selective 5HT3 receptor antagonist has potent antimitogenic and apoptotic effect on HT29 colorectal cancer cell line.
abstract: Serotonin (5-hydroxytryptamine, 5-HT) is known to be a mitogenic factor in several malignancies. It elicits its mitogenic effect through a wide range of 5-HT receptor subtypes and several internal cellular transcription pathways. According to wide distribution of 5-HT3 and 5-HT4 receptors in the gastrointestinal tract, the main aim of this study was to investigate the effect of these receptor agonists and antagonists in a colorectal cell line. In cell culture, we investigated the effects of 5-HT, 5-HT3 and 5-HT4 receptor agonists and antagonists on proliferation of HT29 cells. We also tested apoptosis for the receptor antagonists with TUNEL apoptosis test. In addition, we assayed effects of 5-HT receptor antagonists on cell cycle kinetics with flow cytometery. Proliferation assay revealed that phenylbiguanide (a 5-HT3 receptor selective agonist) increased proliferation of HT29 cells significantly and Y25130 hydrochloride (a 5-HT3 receptor antagonist) had the opposite effect; but for 5-HT4 receptor antagonist, these effects were not significant. In addition, potent apoptotic and cell cycle arresting effect was found for a selective 5-HT3 receptor antagonist but we have not seen any significant effect for the 5-HT4 receptor antagonist. The findings of this study provide strong evidence for the potential role of 5-HT3 receptors in colorectal cancer.
authors.affiliation: Department of Immunology, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ramin
authors.initials: R
authors.lastname: Ataee
authors.forename: Soheila
authors.initials: S
authors.lastname: Ajdary
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Zarrindast
authors.forename: Mehdi
authors.initials: M
authors.lastname: Rezayat
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Shokrgozar
authors.forename: Amin
authors.initials: A
authors.lastname: Ataee
mesh_terms: D050256:Antimitotic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D008856:Microscopy, Fluorescence; D010078:Oxazines / Q000494:pharmacology*; D058827:Serotonin 5-HT3 Receptor Agonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D050256:Antimitotic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D010078:Oxazines; D058827:Serotonin 5-HT3 Receptor Agonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C070671:azasetron