Fenben Lab Fenbendazole and Radiation

Fenben lab fenbendazole is an anthelmintic, which binds to tubulin and disrupts the microtubule equilibrium, preventing polymerization of tubulin in the parasite. Inhibition of this function causes the cell to detach from its microtubules and thereby destroys its viability. Fenbendazole belongs to the class of benzimidazoles and is commonly used in animal experiments to control common helminth infections including ascarids, whipworms, hookworms, and one species of tapeworm. It also has antitumor effects in laboratory animals.

We recently found that fenbendazole caused the death of cancer cells by inhibiting mitosis in vitro. This effect was most dramatic when the fenbendazole treatment was given just before radiation. Our findings indicate that fenbendazole can be combined with radiation to enhance the cytotoxicity of both drugs.

The ability of fenbendazole to prevent radiation-induced cell damage was examined using an established human lymphoma xenograft model in C.B-17/Icr-Prkdcscid/Crl (SCID) mice. This model usually results in 80% to 100% successful tumor growth within 21 d. However, after a facility treatment with fenbendazole diets at our institution, no tumors grew in 40 surviving mice during the 30 d following the injection of a human lymphoma cell line (Apiculuris tetraptera pinworms) and irradiation.

Fenbendazole acted as a moderate microtubule destabilizer and induced cell-cycle arrest in the G2 phase by binding to cyclin B1. The inhibition of cyclin B1 function by fenbendazole was confirmed by an increase in its phosphorylation and degradation by anaphase-promoting complex/cyclin B1 protein kinase (APC/CDK1) during the metaphase-anaphase transition (Fig. 3a).