TY - JOUR
T1 - Aspirin inhibits cancer stem cells properties and growth of glioblastoma multiforme through Rb1 pathway modulation
AU - Pozzoli, Giacomo
AU - Marei, Hany E
AU - Althani, Asma
AU - Boninsegna, Alma
AU - Casalbore, Patrizia
AU - Marlier, Lionel N J L
AU - Lanzilli, Giulia
AU - Zonfrillo, Manuela
AU - Petrucci, Giovanna
AU - Rocca, Bianca
AU - Navarra, Pierluigi
AU - Sgambato, Alessandro
AU - Cenciarelli, Carlo
N1 - © 2019 Wiley Periodicals, Inc.
PY - 2019/1/30
Y1 - 2019/1/30
N2 - 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.
AB - 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.
U2 - 10.1002/jcp.28194
DO - 10.1002/jcp.28194
M3 - Article
C2 - 30701538
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
SN - 1097-4652
ER -