Aspirin inhibits cancer stem cells properties and growth of glioblastoma multiforme through Rb1 pathway modulation.
التاريخ
2019-01-01المؤلف
Pozzoli, GiacomoMarei, Hany E
Althani, Asma
Boninsegna, Alma
Casalbore, Patrizia
Marlier, Lionel N J L
Lanzilli, Giulia
Zonfrillo, Manuela
Petrucci, Giovanna
Rocca, Bianca
Navarra, Pierluigi
Sgambato, Alessandro
Cenciarelli, Carlo
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البيانات الوصفية
عرض كامل للتسجيلةالملخص
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 E 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 and p27 , 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.
المجموعات
- أبحاث مركز البحوث الحيوية الطبية [738 items ]