The article by Glenn and his colleagues, published on January 22 in Science Translational Medicine, demonstrates that the broad-spectrum anthelmintic fenbendazole disrupts normal cellular processes that cancer cells need to grow and spread. The molecule is known to bind to beta-tubulin and prevent its polymerization, inhibiting cell-cycle progression and mitotic catastrophe. This approach could help some patients with resistant cancers, and provides a framework for developing drugs that target the same mechanisms by which certain anticancer agents work.
The research was supported by the National Institutes of Health and Stanford ChEM-H’s Medicinal Chemistry Knowledge Center.
For the first time, a validated HPLC method was used to identify and quantify the active substance in commercial formulations of fenbendazole (USP Apparatus 2, Model RCZ-8B Type Medicine Dissolving Instrument) by comparing three different LOT numbers from each of the two most widely used commercial brands, Brand P and Brand S. The results showed that both fenbendazole samples were effective in the tested cancer cell lines, although the effect was more pronounced with Brand S (Table 1).
Aerobic EMT6 cells were synchronized by serum starvation and treated for 2 or 24 h with 1 uM fenbendazole or vehicle. A 2-h treatment of fenbendazole did not affect the number of cells in monolayer cultures, but 24 h treatment significantly decreased the clonogenicity of these cells. In the dose-response experiments, fenbendazole enhanced the tumor growth inhibitory effect of docetaxel, with both additive and synergistic toxicities, which were confirmed by isobologram analysis.fenbendazole for cancer