The anthelmintic drug fenbendazole has been used commonly to treat rodent pinworm infections, and has had few reported adverse effects on laboratory animals. However, at our institution, a diet containing the compound was incorporated into a sterilizable feed formulated for human lymphoma xenograft models in SCID mice, and resulted in the xenografts failing to grow. This unexpected finding prompted further investigation of the effect of fenbendazole and other commercially available antiparasitic drugs on tumor suppression by radiation. Twenty vendor-supplied 4-wk-old SCID mice were randomized to one of four treatment groups: standard diet, a diet supplemented with supplemental vitamins, a diet supplemented with fenbendazole, and a control group receiving only the standard diet. Tumor growth and radiation responses in these mice were monitored for 6 wk, and the results were statistically analyzed.
The results show that fenbendazole had no significant effect on radiation response either when administered alone or in combination with vitamin supplements. On the other hand, 2-h and 24-h treatments of fenbendazole significantly inhibited the radiation-induced reduction in cell numbers observed in the monolayer cultures of EMT6 cells (Figures 1 and 2), and these results were confirmed using the colony formation assay. In addition, the survival curves of fenbendazole-treated cultures in severe hypoxia showed the same characteristic pattern as that of the cultures treated in air, with rapid and significant loss of viability at low drug concentrations followed by a plateau. This pattern is consistent with the action of fenbendazole on helminthes, which involves binding to and disrupting the tubulin microtubule equilibrium (2, 3). Hypoxia substantially increased the cytotoxic effect of a 2-h treatment of fenbendazole, and this was also apparent when the data were normalized to account for the varying cell number in the treated cultures at time of death. sanare lab fenbendazole