GPER agonist G-1 disrupts tubulin dynamics and potentiates temozolomide to impair glioblastoma cell proliferation

Alex Hirtz (1) , Nolwenn Lebourdais (1) , Fabien Rech (1, 2) , Yann Bailly (1) , Athénaïs Vaginay (1, 3) , Malika Smaïl-Tabbone (3) , Hélène Dubois-Pot-Schneider (1) , Hélène Dumond (1)

1 CRAN - Centre de Recherche en Automatique de Nancy
2 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
3 CAPSID - Computational Algorithms for Protein Structures and Interactions

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: glioblastoma; GPER agonist; G-1; microtubule-targeting agent; microtubule dynamics; proliferation; temozolomide

Domaines: Cancer

Alex Hirtz, Nolwenn Lebourdais, Fabien Rech, Yann Bailly, Athénaïs Vaginay, et al.. GPER agonist G-1 disrupts tubulin dynamics and potentiates temozolomide to impair glioblastoma cell proliferation. Cells, 2021, 10, pp.3438. ⟨10.3390/cells10123438⟩. ⟨hal-03472082⟩