We studied the effect of fenbendazole, a widely used antihelminth with mechanisms that overlap with those of hypoxia-selective nitroheterocyclic cytotoxins and radiosensitizers, on radiation sensitivity in EMT6 mammary tumor cells in vitro and in mouse tumors. 2- and 24-h treatments with fenbendazole reduced yield-corrected surviving fractions but did not alter the radiation dose-response curves.
Antihelminthic
Fenbendazole, also known as pancur or safe guard is a drug used to treat parasites and worms in animals (roundworms, hookworms, whipworms, and tapeworms). It is a member of the benzimidazole family of anthelmintics and has a broad spectrum anthelmintic effect. It acts by destroying the microtubules of parasitic worms and disrupting their energy processes.
It is believed that fenbendazole may have anti-cancer effects by disrupting the microtubule balance in cancer cells. It is also believed to block the tumors’ ability to process sugar, which they need for survival.
During a study at our institution, we found that fenbendazole suppressed the growth of human lymphoma xenografts in SCID mice. The fenbendazole was incorporated into a sterilizable diet that was supplemented with vitamins to compensate for loss during dietary sterilization. The fenbendazole-containing diet was compared to a control diet without fenbendazole or vitamin supplements. Results showed that neither fenbendazole nor the supplemented vitamins significantly affected the growth of unirradiated or irradiated EMT6 tumors.
Anticancer
Fenbendazole is a deworming drug that has shown promising results in the treatment of some cancers. It is part of a group of drugs known as the benzimidazole carbamate (BZ) class. It works by disrupting the cellular processes that viruses and some cancer cells use to grow and spread.
A study conducted by Stanford researchers showed that combining fenbendazole with quercetin can further limit the multiplication of cancer cells and prevent their spread. This combination also boosted the activity of the gene p53, which is a tumor suppressor.
In the study, mice with EMT6 mammary tumors were injected i.p. with fenbendazole or a placebo before receiving radiation. The researchers found that fenbendazole had cytotoxic and antitumor effects, which were enhanced by the combination of irradiation and fenbendazole. The toxicity of fenbendazole increased with the length of incubation and under conditions of severe hypoxia. Its mechanisms of action overlapped with those of the hypoxia-selective nitroheterocyclic cytotoxins/radiosensitizers and taxanes.
Immunosuppressant
A recent study published in the journal Nature Medicine showed that fenbendazole, an antihelminthic drug commonly used to treat pinworms, can also suppress tumor growth. The research was conducted in mice that received fenbendazole along with other supplements and a nutrient-rich diet. The result was that the xenografts did not grow after eight weeks of treatment.
2-h treatments with fenbendazole did not significantly affect cell numbers in aerobic EMT6 monolayer cultures, even at doses that approached the limit of solubility (Figure 1). Severe hypoxia increased the toxicity of fenbendazole to cells, but cell viability was restored to near-normal levels at high drug concentrations.
In addition, fenbendazole did not alter the radiation response of aerobic or hypoxic EMT6 cells in vitro (Figure 2). This finding was consistent with tumor data from mice receiving a fenbendazole-containing diet.
Antifungal
Fenbendazole is a highly effective antifungal drug, especially against Cryptococcus. It acts through a mechanism similar to that of flubendazole in nematodes: binding to b-tubulin, resulting in local unfolding and an abnormal conformation that prevents the polymerization of a- and b-tubulin subunits to form microtubules. This effect has been shown to be fungicidal in a number of fungal models, including C. neoformans and C. gattii. It also appears to inhibit urease production in these fungal species, which is an important property of the drug for treating animal cryptococcosis.
To test the fungicidal properties of fenbendazole, C57BL/6 mice were intranasally administered with a solution containing a range of fenbendazole concentrations and varying concentrations of amphotericin B. The fungicidal activity of the drugs was assessed using a checkerboard assay, and the results showed that fenbendazole is fungicidal at the MIC against both C. neoformans H99 and C. gattii R265. The drug was also found to reduce intracellular proliferation rates in phagocytized macrophages, which is associated with reduced virulence (28).sanare lab fenbendazole
