Effects mediated by M2 muscarinic orthosteric agonist on cell growth in human neuroblastoma cell lines
| Autor: | Ada Maria Tata, Elisa Damo, Luciana Dini, Francesca Romana Mattei, Anna Maria Lucianò, Elisa Panzarini |
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| Přispěvatelé: | Luciano, A. M., Mattei, F., Damo, E., Panzarini, E., Dini, L., Tata, A. M. |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Agonist medicine.drug_class General Chemical Engineering M2 receptors cell proliferation M2 receptors neuroblastoma orthosteric ligand survival Neuroblastoma cell 03 medical and health sciences 0302 clinical medicine Neuroblastoma Muscarinic acetylcholine receptor medicine Chemistry Cell growth Muscarinic acetylcholine receptor M2 General Chemistry medicine.disease Eurasia 2018 030104 developmental biology cell proliferation Cancer research M2 receptor 030217 neurology & neurosurgery |
| Popis: | The role of muscarinic receptors has been largely documented over the past few decades. Recently we demonstrated that the activation of M2 muscarinic receptors arrested cell proliferation and induced apoptosis in glioblastoma and in other tumour types. This paper aims to evaluate the expression of the M2 muscarinic receptor subtypes in different neuroblastoma cell lines and its role in the control of cell proliferation and survival. Neuroblastoma is the most common solid extracranial tumour, appearing during childhood and displaying a differentiated clinical behaviour. Considering the high homology between muscarinic receptor subtypes, we have identified Arecaidine Propargyl Ester (APE) as a selective orthosteric agonist for M2 muscarinic receptors. Using this agonist, we demonstrate how a selective activation of the M2 receptor subtype negatively modulates cell growth without affecting cell survival in different human neuroblastoma cell lines. As similarly demonstrated in other cell types, following the M2 receptor silencing by short-interference RNA, the effects of APE are completely abolished. We conclude by confirming the ability of APE to bind selectively M2 muscarinic receptor subtypes. Moreover, for the first time we demonstrate that M2 receptor activation inhibits cell growth also in human neuroblastoma cells, indicating that M2 receptors may be an interesting therapeutic target in several solid tumours. |
| Databáze: | OpenAIRE |
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