1. Aspirin inhibits cancer stem cells properties and growth of glioblastoma multiforme through Rb1 pathway modulation
- Author
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Giacomo Pozzoli 1, 2, Hany E. Marei 3, Asma Althani 4, Alma Boninsegna 5, Patrizia Casalbore 6, Lionel NJL. Marlier 7, Giulia Lanzilli 7, Manuela Zonfrillo 7, Giovanna Petrucci 1, Bianca Rocca 1, Pierluigi Navarra 1, Alessandro Sgambato 5, and Carlo Cenciarelli 7
- Subjects
0301 basic medicine ,Settore BIO/14 - FARMACOLOGIA ,aspirin ,Physiology ,Clinical Biochemistry ,Population ,GBM ,CSC ,Settore MED/05 - PATOLOGIA CLINICA ,stemness ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cancer stem cell ,Medicine ,Rb1 ,education ,Aspirin ,education.field_of_study ,Settore MED/06 - ONCOLOGIA MEDICA ,business.industry ,Cell growth ,Cox ,Cancer ,Cell Biology ,medicine.disease ,030104 developmental biology ,chemistry ,Tumor progression ,030220 oncology & carcinogenesis ,Cancer research ,Growth inhibition ,Stem cell ,business ,medicine.drug - Abstract
Several clinical studies indicated that the daily use of aspirin (acetylsalicylic acid, ASA) reduces the cancer risk via Cyclooxygenases (Cox-1 and Cox-2) inhibition. In addition, aspirin-induced Cox-dependent and independent anti-tumor 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 to reduced cell proliferation and motility. Aspirin did not interfere with cell viability but induced cell-cycle arrest. Exogenous Prostaglandin E2 (PGE2) 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 p21waf1 and p27Kip1, associated with a reduction of CyclinD1 and Rb1 protein phosphorylation, and involve the down-regulation of key molecules responsible of tumor development, i.e. Notch1, Sox2, Stat3 and Survivin. Our results support a possible role of aspirin as an adjunctive therapy in the clinical management of GBM patients.
- Published
- 2018