1. Resveratrol impairs glioma stem cells proliferation and motility by modulating the wnt signaling pathway
- Author
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Riccardo Bazzoni, Leda Dalprà, Mario Strazzabosco, Marialuisa Lavitrano, Gabriele Romano, Roberto Giovannoni, Angela Bentivegna, Chiara Cilibrasi, Laura Paoletta, Massimiliano Cadamuro, Gabriele Riva, Valentina Butta, Cilibrasi, C, Riva, G, Romano, G, Cadamuro, M, Bazzoni, R, Butta, V, Paoletta, L, Dalpra', L, Strazzabosco, M, Lavitrano, M, Giovannoni, R, and Bentivegna, A
- Subjects
Genetics and Molecular Biology (all) ,Brain Neoplasms ,Cell Line, Tumor ,Cell Movement ,Cell Proliferation ,Cell Survival ,Epithelial-Mesenchymal Transition ,Glioma ,Humans ,Neoplastic Stem Cells ,Proto-Oncogene Proteins c-myc ,Resveratrol ,Stilbenes ,Wnt Signaling Pathway ,beta Catenin ,0301 basic medicine ,Cell ,lcsh:Medicine ,Gene Expression ,Medicine (all) ,Biochemistry ,Agricultural and Biological Sciences (all) ,Tumor initiation ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Signaling ,Drug Metabolism ,Medicine and Health Sciences ,Blastomas ,Enzyme assays ,Colorimetric assays ,lcsh:Science ,Neurological Tumors ,Bioassays and physiological analysis ,WNT Signaling Cascade ,Tumor ,Multidisciplinary ,MTT assay ,Wnt signaling pathway ,Catenins ,Signaling Cascades ,3. Good health ,Cell biology ,Cell Motility ,medicine.anatomical_structure ,Oncology ,Neurology ,030220 oncology & carcinogenesis ,Stem cell ,Research Article ,Signal Transduction ,Cell Physiology ,Motility ,Biology ,Cell Line ,03 medical and health sciences ,medicine ,Genetics ,Pharmacokinetics ,Pharmacology ,Biochemistry, Genetics and Molecular Biology (all) ,Cell growth ,lcsh:R ,Biology and Life Sciences ,Cancers and Neoplasms ,Proteins ,Cell Biology ,medicine.disease ,Cell Metabolism ,Research and analysis methods ,Cytoskeletal Proteins ,030104 developmental biology ,chemistry ,Biochemical analysis ,lcsh:Q ,Glioblastoma Multiforme - 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.
- Published
- 2017