Antiparasitic mebendazole shows survival benefit in 2 preclinical models of glioblastoma multiforme

Research output: Contribution to journalArticle

Abstract

Glioblastoma multiforme (GBM) is the most common and aggressive brain cancer, and despite treatment advances, patient prognosis remains poor. During routine animal studies, we serendipitously observed that fenbendazole, a benzimidazole antihelminthic used to treat pinworm infection, inhibited brain tumor engraftment. Subsequent in vitro and in vivo experiments with benzimidazoles identified mebendazole as the more promising drug for GBM therapy. In GBM cell lines, mebendazole displayed cytotoxicity, with half-maximal inhibitory concentrations ranging from 0.1 to 0.3 μM. Mebendazole disrupted microtubule formation in GBM cells, and in vitro activity was correlated with reduced tubulin polymerization. Subsequently, we showed that mebendazole significantly extended mean survival up to 63% in syngeneic and xenograft orthotopic mouse glioma models. Mebendazole has been approved by the US Food and Drug Administration for parasitic infections, has a long track-record of safe human use, and was effective in our animal models with doses documented as safe in humans. Our findings indicate that mebendazole is a possible novel anti-brain tumor therapeutic that could be further tested in clinical trials.

Original languageEnglish (US)
Pages (from-to)974-982
Number of pages9
JournalNeuro-Oncology
Volume13
Issue number9
DOIs
StatePublished - Sep 2011

Fingerprint

Mebendazole
Antiparasitic Agents
Glioblastoma
Survival
Brain Neoplasms
Fenbendazole
Enterobius
Benzimidazoles
Parasitic Diseases
United States Food and Drug Administration
Tubulin
Heterografts
Glioma
Microtubules
Polymerization
Therapeutics
Animal Models
Clinical Trials
Cell Line
Infection

Keywords

  • Albendazole
  • Animal models
  • Antiparasitic
  • Benzimidazole
  • Drugdiscovery
  • Glioblastoma
  • Mebendazole
  • Preclinical trial
  • Tubulin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Clinical Neurology

Cite this

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title = "Antiparasitic mebendazole shows survival benefit in 2 preclinical models of glioblastoma multiforme",
abstract = "Glioblastoma multiforme (GBM) is the most common and aggressive brain cancer, and despite treatment advances, patient prognosis remains poor. During routine animal studies, we serendipitously observed that fenbendazole, a benzimidazole antihelminthic used to treat pinworm infection, inhibited brain tumor engraftment. Subsequent in vitro and in vivo experiments with benzimidazoles identified mebendazole as the more promising drug for GBM therapy. In GBM cell lines, mebendazole displayed cytotoxicity, with half-maximal inhibitory concentrations ranging from 0.1 to 0.3 μM. Mebendazole disrupted microtubule formation in GBM cells, and in vitro activity was correlated with reduced tubulin polymerization. Subsequently, we showed that mebendazole significantly extended mean survival up to 63{\%} in syngeneic and xenograft orthotopic mouse glioma models. Mebendazole has been approved by the US Food and Drug Administration for parasitic infections, has a long track-record of safe human use, and was effective in our animal models with doses documented as safe in humans. Our findings indicate that mebendazole is a possible novel anti-brain tumor therapeutic that could be further tested in clinical trials.",
keywords = "Albendazole, Animal models, Antiparasitic, Benzimidazole, Drugdiscovery, Glioblastoma, Mebendazole, Preclinical trial, Tubulin",
author = "Renyuan Bai and Verena Staedtke and Aprhys, {Colette M.} and Gallia, {Gary L} and Riggins, {Gregory J}",
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AU - Riggins, Gregory J

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