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Article

GPER Agonist G-1 Disrupts Tubulin Dynamics and Potentiates Temozolomide to Impair Glioblastoma Cell Proliferation

by
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,† and
Hélène Dumond
1,*,†
1
Université de Lorraine, CNRS, CRAN, F-54000 Nancy, France
2
Université de Lorraine, CHRU-Nancy, Service de Neurochirurgie, F-54000 Nancy, France
3
Université de Lorraine, CNRS, Inria, LORIA, F-54000 Nancy, France
*
Author to whom correspondence should be addressed.
†
Hélène Dubois-Pot-Schneider and Hélène Dumond co-supervised this work.
Cells 2021, 10(12), 3438; https://doi.org/10.3390/cells10123438
Submission received: 14 October 2021 / Revised: 29 November 2021 / Accepted: 3 December 2021 / Published: 7 December 2021
(This article belongs to the Special Issue Glioblastoma Cell: From Molecular Target to Innovative Therapy)
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Abstract

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

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MDPI and ACS Style

Hirtz, A.; Lebourdais, N.; Rech, F.; Bailly, Y.; Vaginay, A.; Smaïl-Tabbone, M.; Dubois-Pot-Schneider, H.; Dumond, H. GPER Agonist G-1 Disrupts Tubulin Dynamics and Potentiates Temozolomide to Impair Glioblastoma Cell Proliferation. Cells 2021, 10, 3438. https://doi.org/10.3390/cells10123438

AMA Style

Hirtz A, Lebourdais N, Rech F, Bailly Y, Vaginay A, Smaïl-Tabbone M, Dubois-Pot-Schneider H, Dumond H. GPER Agonist G-1 Disrupts Tubulin Dynamics and Potentiates Temozolomide to Impair Glioblastoma Cell Proliferation. Cells. 2021; 10(12):3438. https://doi.org/10.3390/cells10123438

Chicago/Turabian Style

Hirtz, Alex, Nolwenn Lebourdais, Fabien Rech, Yann Bailly, Athénaïs Vaginay, Malika Smaïl-Tabbone, Hélène Dubois-Pot-Schneider, and Hélène Dumond. 2021. "GPER Agonist G-1 Disrupts Tubulin Dynamics and Potentiates Temozolomide to Impair Glioblastoma Cell Proliferation" Cells 10, no. 12: 3438. https://doi.org/10.3390/cells10123438

APA Style

Hirtz, A., Lebourdais, N., Rech, F., Bailly, Y., Vaginay, A., Smaïl-Tabbone, M., Dubois-Pot-Schneider, H., & Dumond, H. (2021). GPER Agonist G-1 Disrupts Tubulin Dynamics and Potentiates Temozolomide to Impair Glioblastoma Cell Proliferation. Cells, 10(12), 3438. https://doi.org/10.3390/cells10123438

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