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.
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Authors | Ren-Yuan Bai, Verena Staedtke, Colette M Aprhys, Gary L Gallia, Gregory J Riggins |
Journal | Neuro-oncology
(Neuro Oncol)
Vol. 13
Issue 9
Pg. 974-82
(Sep 2011)
ISSN: 1523-5866 [Electronic] England |
PMID | 21764822
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antinematodal Agents
- Tubulin
- Mebendazole
- Luciferases
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Topics |
- Animals
- Antinematodal Agents
(therapeutic use)
- Apoptosis
(drug effects)
- Blotting, Western
- Brain Neoplasms
(drug therapy, mortality, pathology)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Disease Models, Animal
- Female
- Fluorescent Antibody Technique
- Glioblastoma
(drug therapy, mortality, pathology)
- Humans
- Luciferases
(metabolism)
- Mebendazole
(therapeutic use)
- Mice
- Mice, Inbred C57BL
- Mice, Nude
- Survival Rate
- Tubulin
(metabolism)
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