Radiosensitizing Effects of Fenbendazole

Fenbendazole is a widely used antihelminthic drug with mechanisms of action that overlap with those of hypoxia-selective nitroheterocyclic cytotoxins/radiosensitizers and taxanes. It was found to have radiosensitizing properties in a series of cell culture and solid tumor studies using the EMT6 human lymphoma xenograft. The xenografts are susceptible to radiation-induced growth inhibition and often achieve 80% to 100% tumor regression within 21 d following injection. During an 8-wk facility treatment for Aspiculuris tetraptera pinworms at our institution, fenbendazole diets were fed to the mice, and none of the 40 mice developed xenograft tumors during 30 d of fenbendazole feeding. To determine whether fenbendazole alone had radiosensitizing properties, this agent was given in three daily i.p. injections to mice bearing EMT6 tumors. Tumor growth was not inhibited by fenbendazole alone. Irradiation of these tumors with 10 Gy produced a significant inhibition of tumor growth, but the effect was unaffected by three daily i.p. fenbendazole treatments administered one day before, 2 h before, and 1 day after irradiation of the tumors. The dose-response curves for aerobic and hypoxic cells treated with fenbendazole were identical.

It is possible that the initial observation of a radiosensitizing effect of fenbendazole was due to vitamin concentrations in the study diet. The diet used during the initial observation had a 6-mo expiration date, and vitamin concentrations tend to deteriorate over time. However, the study diet used during the subsequent experiment was less than a week old and likely had higher vitamin concentrations than those in the original observation diet.sanare lab fenbendazole