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

• Published in: Neuro-oncology (Charlottesville, Va.) Vol. 13; no. 9; pp. 974 - 982
• Main Authors: Bai, Ren-Yuan, Staedtke, Verena, Aprhys, Colette M., Gallia, Gary L., Riggins, Gregory J.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-09-2011
• Subjects: Animals; Antinematodal Agents - therapeutic use; Apoptosis - drug effects; Basic and Translational Investigations; Blotting, Western; Brain Neoplasms - drug therapy; Brain Neoplasms - mortality; Brain Neoplasms - pathology; Cell Line, Tumor; Cell Proliferation - drug effects; Disease Models, Animal; Female; Fluorescent Antibody Technique; Glioblastoma - drug therapy; Glioblastoma - mortality; Glioblastoma - pathology; Humans; Luciferases - metabolism; Mebendazole - therapeutic use; Mice; Mice, Inbred C57BL; Mice, Nude; Survival Rate; Tubulin - metabolism; animal models; glioblastoma; drug discovery; albendazole; tubulin; antiparasitic; benzimidazole; mebendazole; preclinical trial
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/nor077

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.