The benzimidazole antiparasitic agent fenbendazole (methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl) carbamate) is used for its broad spectrum anthelmintic activity against pinworms, hookworms, giardia, roundworms, Taenia solium and pulmonary paragonimiasis in various animal species. It exerts its anthelmintic effect by binding to the b-tubulin subunits of microtubules and disrupting their polymerization. This property of fenbendazole makes it a candidate for repurposing as an anticancer drug.
Recent studies have shown that fenbendazole has moderate microtubule depolymerizing activity and a potent antitumor effect in several cancer cell lines, and is a potential radiosensitizer. We tested whether this activity can be enhanced in hypoxic cells. In 2-h treatments, fenbendazole exhibited high cytotoxicity in hypoxic cultures, while it showed no toxicity in aerobic cultures. Severe hypoxia augmented the fenbendazole cytotoxicity in these cultures, and a dose-response curve with normalized surviving fractions was obtained. In contrast to results obtained for fenbendazole alone, treatment with fenbendazole and docetaxel produced additive cytotoxicity in these cells.
In a parallel experiment, we investigated the effect of three daily i.p. injections of fenbendazole 50 mg/kg/day in BALB/cRw mice containing EMT6 tumors. As shown in the Table, neither the growth nor radiation response of these tumors was affected by fenbendazole treatment, and this finding was confirmed when the same three-injection fenbendazole regimen was administered to tumor-bearing mice prior to irradiation. Points are geometric means+-SEM; 7-8 mice/group. fenben lab fenbendazol