GPER Agonist G-1 Disrupts Tubulin Dynamics and Potentiates Temozolomide to Impair Glioblastoma Cell Proliferation.
Fiche publication
Date publication
décembre 2021
Journal
Cells
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BAILLY Yannick, Dr DUBOIS-POT-SCHNEIDER Hélène, Dr DUMOND Hélène, Dr RECH Fabien
Tous les auteurs :
Hirtz A, Lebourdais N, Rech F, Bailly Y, Vaginay A, Smaïl-Tabbone M, Dubois-Pot-Schneider H, Dumond H
Lien Pubmed
Résumé
Glioblastoma (GBM) is the most common brain tumor in adults, which is very aggressive, with a very poor prognosis that affects men twice as much as women, suggesting that female hormones (estrogen) play a protective role. With an in silico approach, we highlighted that the expression of the membrane G-protein-coupled estrogen receptor (GPER) had an impact on GBM female patient survival. In this context, we explored for the first time the role of the GPER agonist G-1 on GBM cell proliferation. Our results suggested that G-1 exposure had a cytostatic effect, leading to reversible G2/M arrest, due to tubulin polymerization blockade during mitosis. However, the observed effect was independent of GPER. Interestingly, G-1 potentiated the efficacy of temozolomide, the current standard chemotherapy treatment, since the combination of both treatments led to prolonged mitotic arrest, even in a temozolomide less-sensitive cell line. In conclusion, our results suggested that G-1, in combination with standard chemotherapy, might be a promising way to limit the progression and aggressiveness of GBM.
Mots clés
G-1, GPER agonist, glioblastoma, microtubule dynamics, microtubule-targeting agent, proliferation, temozolomide
Référence
Cells. 2021 12 7;10(12):