title: Resveratrol Impairs Glioma Stem Cells Proliferation and Motility by Modulating the Wnt Signaling Pathway.
abstract: Glioblastoma multiforme (GBM) is a grade IV astrocytoma and the most common form of malignant brain tumor in adults. GBM remains one of the most fatal and least successfully treated solid tumors: current therapies provide a median survival of 12-15 months after diagnosis, due to the high recurrence rate. Glioma Stem Cells (GSCs) are believed to be the real driving force of tumor initiation, progression and relapse. Therefore, better therapeutic strategies GSCs-targeted are needed. Resveratrol is a polyphenolic phytoalexin found in fruits and vegetables displaying pleiotropic health benefits. Many studies have highlighted its chemo-preventive and chemotherapeutic activities in a wide range of solid tumors. In this work, we analyzed the effects of Resveratrol exposure on cell viability, proliferation and motility in seven GSC lines isolated from GBM patients. For the first time in our knowledge, we investigated Resveratrol impact on Wnt signaling pathway in GSCs, evaluating the expression of seven Wnt signaling pathway-related genes and the protein levels of c-Myc and β-catenin. Finally, we analyzed Twist1 and Snail1 protein levels, two pivotal activators of epithelial-mesenchymal transition (EMT) program. Results showed that although response to Resveratrol exposure was highly heterogeneous among GSC lines, generally it was able to inhibit cell proliferation, increase cell mortality, and strongly decrease cell motility, modulating the Wnt signaling pathway and the EMT activators. Treatment with Resveratrol may represent a new interesting therapeutic approach, in order to affect GSCs proliferation and motility, even if further investigations are needed to deeply understand the GSCs heterogeneous response.
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, via Cadore, Monza, Italy.|PhD Program in Neuroscience, University of Milano-Bicocca, via Cadore, Monza, Italy.|NeuroMI, Milan center of Neuroscience, University of Milano Bicocca, Dept. of Neurology and Neuroscience, San Gerardo Hospital, via Pergolesi, Monza, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cilibrasi
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, via Cadore, Monza, Italy.|PhD Program in Neuroscience, University of Milano-Bicocca, via Cadore, Monza, Italy.|NeuroMI, Milan center of Neuroscience, University of Milano Bicocca, Dept. of Neurology and Neuroscience, San Gerardo Hospital, via Pergolesi, Monza, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Riva
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, via Cadore, Monza, Italy.|PhD Program in Translational and Molecular Medicine (DIMET), University of Milano-Bicocca, via Cadore, Monza, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Romano
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, via Cadore, Monza, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cadamuro
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, via Cadore, Monza, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bazzoni
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, via Cadore, Monza, Italy.|PhD Program in Neuroscience, University of Milano-Bicocca, via Cadore, Monza, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Butta
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, via Cadore, Monza, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Paoletta
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, via Cadore, Monza, Italy.
authors.forename: Leda
authors.initials: L
authors.lastname: Dalprà
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, via Cadore, Monza, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Strazzabosco
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, via Cadore, Monza, Italy.
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Lavitrano
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, via Cadore, Monza, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Giovannoni
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, via Cadore, Monza, Italy.|NeuroMI, Milan center of Neuroscience, University of Milano Bicocca, Dept. of Neurology and Neuroscience, San Gerardo Hospital, via Pergolesi, Monza, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Bentivegna
mesh_terms: D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D013267:Stilbenes; D051176:beta Catenin; D000077185:Resveratrol