Fenbendazole As an Anticancer Agent
Fenbendazole, an antiparasitic drug used extensively in rodent pinworm treatments, is well known to interfere with microtubule assembly and growth in parasite cells. It is also a weak alkylating agent with the chemical structure that resembles that of compounds known to act as radiosensitizers. Because of these similarities, fenbendazole is under study for its potential value as an anticancer agent (1–3).
Recently, during a facility treatment for Aspiculuris tetraptera pinworms with fenbendazole diet at our institution, the established human lymphoma xenograft model in C.B-17/Icr-Prkdcscid/Crl (SCID) mice failed to grow in the treated group, and the authors speculated that fenbendazole might have been responsible because of its reported effect on radiation response (4, 5).
To examine the effect of fenbendazole on cellular viability, cultures were made hypoxic by sealing the culture bottles with rubber gaskets, inserting needles for influx and efflux of gases, and then gassing with a humidified mixture of 95% nitrogen and 5% CO2 containing 1 ppm oxygen (8–9). Using these conditions, a solution of 10 mM fenbendazole was administered to the cultures by injection through the gaskets without breaking the hypoxia and incubated for 2 h. After incubation, the cultures were exposed to graded doses of radiation in aerobic or hypoxic conditions and analyzed for cell survival in a colony formation assay (6–8).
We found that fenbendazole significantly inhibited the radiation response of hypoxic cells, but did not alter that of aerobic cells in this experimental system. This observation is consistent with the hypothesis that fenbendazole and other similar compounds might act as radiosensitizers by binding to the microtubules of cancer cells to prevent polymerization. sanare lab fenbendazole