Aspirin inhibits cancer stem cells properties and growth of glioblastoma multiforme through Rb1 pathway modulation |
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| Authors: | Giacomo Pozzoli Hany E. Marei Asma Althani Alma Boninsegna Patrizia Casalbore Lionel N. J. L. Marlier Giulia Lanzilli Manuela Zonfrillo Giovanna Petrucci Bianca Rocca Pierluigi Navarra Alessandro Sgambato Carlo Cenciarelli |
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| Affiliation: | 1. Institute of Pharmacology, Università Cattolica del Sacro Cuore, Rome, Italy;2. Department of Cytology and Histology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt;3. Biomedical Research Center, Qatar University, Doha, Qatar;4. Institute of General Pathology, Università Cattolica del Sacro Cuore, Rome, Italy;5. Department of Biomedical Sciences, Institute of Cell Biology and Neurobiology (IBCN), National Research Council (CNR), Rome, Italy;6. Department of Biomedical Sciences, Institute of Translational Pharmacology (IFT), National Research Council (CNR), Rome, Italy;7. Institute of Pharmacology, Università Cattolica del Sacro Cuore, Rome, Italy Pharmacology Unit, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy |
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| Abstract: | Several clinical studies indicated that the daily use of aspirin or acetylsalicylic acid reduces the cancer risk via cyclooxygenases (Cox-1 and Cox-2) inhibition. In addition, aspirin-induced Cox-dependent and -independent antitumor effects have also been described. Here we report, for the first time, that aspirin treatment of human glioblastoma cancer (GBM) stem cells, a small population responsible for tumor progression and recurrence, is associated with reduced cell proliferation and motility. Aspirin did not interfere with cell viability but induced cell-cycle arrest. Exogenous prostaglandin E2 significantly increased cell proliferation but did not abrogate the aspirin-mediated growth inhibition, suggesting a Cox-independent mechanism. These effects appear to be mediated by the increase of p21 waf1 and p27 Kip1, associated with a reduction of Cyclin D1 and Rb1 protein phosphorylation, and involve the downregulation of key molecules responsible for tumor development, that is, Notch1, Sox2, Stat3, and Survivin. Our results support a possible role of aspirin as adjunctive therapy in the clinical management of GBM patients. |
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| Keywords: | aspirin Cox CSC GBM Rb1 stemness |
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