title: The activation of M2 muscarinic receptor inhibits cell growth and survival in human glioblastoma cancer stem cells.
abstract: The involvement of muscarinic receptors in cancer has been reported. Recently we have demonstrated that the activation of M2 muscarinic receptors, through arecaidine propargyl ester, arrests cell proliferation and induces apoptosis in primary and established glioblastoma cell lines. Considering the inability of conventional drugs to completely counteract the growth of glioblastoma cancer stem cells (GSCs), we have investigated the effect produced by arecaidine on GSC growth and survival. The expression of M2 receptors has been analyzed in GSC cell lines derived from human biopsies. Based on the M2 receptor expression levels, we have selected two gliolastoma cell lines (GB7 and GB8). In both cell lines the treatment with arecaidine decreased GCS cell growth. GB7 cells exhibited a time- and dose-dependent decrease of cell proliferation. Moreover arecaidine caused a reduced cell survival in particular in GB8 cell line. These effects appear to be mediated by M2 receptor activation as suggested by pharmacological experiments performed in the presence of M1 and M3 preferring antagonists (pirenzepine and 4-DAMP respectively) and M2/M4 antagonist methoctramine. M2 receptor silencing by siRNA has further confirmed that the inhibition of cell growth arecaidine-induced was mediated by the M2 receptor activation. These results suggest that the M2 receptors may represent a new interesting therapeutic tool to counteract glioblastoma cancer stem cell growth and survival.
authors.affiliation: Dept. of Biology and Biotechnologies C. Darwin, Research Center of Neurobiology Daniel Bovet, "Sapienza" University of Rome, Roma, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Alessandrini
authors.affiliation: Dept. of Biology and Biotechnologies C. Darwin, Research Center of Neurobiology Daniel Bovet, "Sapienza" University of Rome, Roma, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cristofaro
authors.affiliation: Dept. of Biology and Biotechnologies C. Darwin, Research Center of Neurobiology Daniel Bovet, "Sapienza" University of Rome, Roma, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Di Bari
authors.affiliation: Centre for Integrative Biology, Università degli Studi di Trento, Trento, Italy.
authors.forename: Jacopo
authors.initials: J
authors.lastname: Zasso
authors.affiliation: Centre for Integrative Biology, Università degli Studi di Trento, Trento, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Conti
authors.affiliation: Dept. of Biology and Biotechnologies C. Darwin, Research Center of Neurobiology Daniel Bovet, "Sapienza" University of Rome, Roma, Italy. Electronic address: adamaria.tata@uniroma1.it.
authors.forename: Ada Maria
authors.initials: AM
authors.lastname: Tata
mesh_terms: D015415:Biomarkers; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D043585:Receptor, Muscarinic M2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D043585:Receptor, Muscarinic M2
keywords: Cancer stem cells; Cell death; Glioblastoma; M2 receptors; Proliferation