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Low concentrations of vorinostat decrease EB1 expression in GBM cells and affect microtubule dynamics, cell survival

Thomas Perez1,2, Raphaël Bergès1, Hélène Maccario1

  • 1Aix-Marseille University, CNRS, INP, Institute of NeuroPhysiopathology, Marseille, France.

Oncotarget
|March 4, 2021
PubMed

Insights

Low-dose vorinostat shows new anticancer effects against glioblastoma multiforme (GBM) by targeting microtubules and reducing EB1 expression, potentially offering a more selective treatment option with fewer side effects.

Area of Science:

  • Neuro-oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Glioblastoma multiforme (GBM) is an aggressive brain tumor with high mortality.
  • Histone deacetylase inhibitors (HDACi) show promise but lack selectivity, causing side effects.
  • EB1 overexpression is a known marker of poor prognosis in GBM.

Purpose of the Study:

  • To investigate the novel anticancer properties and mechanisms of low-dose vorinostat in GBM cells.
  • To explore vorinostat's effects on microtubule dynamics and EB1 expression in GBM.
  • To assess the therapeutic potential of low-dose vorinostat for GBM, particularly in EB1-overexpressing tumors.

Main Methods:

  • Treatment of various GBM cells with low concentrations of vorinostat.
  • Analysis of tubulin acetylation and detyrosination.
  • Assessment of the impact on microtubule plus-end stabilizing caps (EB proteins) and microtubule dynamics.
  • Evaluation of EB1 expression levels in response to vorinostat treatment.

Main Results:

  • Low-dose vorinostat affects the microtubule cytoskeleton in a non-histone 3 (H3) manner.
  • Vorinostat induces tubulin acetylation and detyrosination, impacting microtubule stability.
  • The drug suppresses microtubule dynamic instability by affecting EB stabilizing caps.
  • A significant decrease in EB1 expression was observed in GBM cells treated with vorinostat.

Conclusions:

  • Low-dose vorinostat, potentially selective for HDAC6, exhibits novel anticancer mechanisms in GBM.
  • Vorinostat's ability to decrease EB1 expression is a significant finding for GBM therapy.
  • This approach may offer a more targeted and less toxic therapeutic option for GBM patients, especially those with EB1 overexpression.
  • Further clinical trials are warranted to validate these findings.
Keywords:
EB1glioblastomamicrotubuletubulinvorinostat

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