Low concentrations of vorinostat decrease EB1 expression in GBM cells and affect microtubule dynamics, cell survival and migration
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Thomas Perez1,2, Raphaël Bergès1, Hélène Maccario1, Sarah Oddoux1 and Stéphane Honoré1,2
1 Aix-Marseille University, CNRS, INP, Institute of NeuroPhysiopathology, Marseille, France
2 APHM, Hôpital de la Timone, Service Pharmacie, Marseille, France
Keywords: vorinostat; glioblastoma; EB1; microtubule; tubulin
Received: September 21, 2020 Accepted: February 01, 2021 Published: February 16, 2021
Glioblastoma multiform (GBM) is the most frequent primitive brain tumor with a high recurrence and mortality. Histone deacetylase inhibitors (HDACi) have evoked great interest because they are able to change transcriptomic profiles to promote tumor cell death but also induce side effects due to the lack of selectivity. We show in this paper new anticancer properties and mechanisms of action of low concentrations of vorinostat on various GBM cells which acts by affecting microtubule cytoskeleton in a non-histone 3 (H3) manner. Indeed, vorinostat induces tubulin acetylation and detyrosination, affects EB stabilizing cap on microtubule plus ends and suppresses microtubule dynamic instability. We previously identified EB1 overexpression as a marker of bad prognostic in GBM. Interestingly, we show for the first time to our knowledge, a strong decrease of EB1 expression in GBM cells by a drug. Altogether, our results suggest that low dose vorinostat, which is more selective for HDAC6 inhibition, could therefore represent an interesting therapeutic option for GBM especially in patients with EB1 overexpressing tumor with lower expected side effects. A validation of our hypothesis is needed during future clinical trials with this drug in GBM.
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