Fenbendazole, also known as Fenben or Benben, is an anthelmintic that has been safely used in humans and animals to treat parasitic infections for over six decades. It belongs to a broad group of antihelmintic drugs called the benzimidazole carbamate family, which were first developed as broad-spectrum anthelmintics in the 1950s and 1960s. There are three members of this family in human clinical use, fenbendazole, albendazole and mebendazole.
These antihelmintic drugs are very effective and safe at a low dosage. At higher doses, they can have a variety of adverse effects including liver and intestinal damage, dizziness, headache, nausea, vomiting, skin rashes and depression. In animal studies, fenbendazole has also been shown to inhibit the growth of several cancer cell types.
Previous work from our laboratory and others demonstrated that fenbendazole was toxic to EMT6 tumor cells in vitro, with a steep reduction of cell numbers in monolayer cultures at drug concentrations well below the limit of solubility. These cell viability curves were not altered by varying the duration of drug treatment, even with a 24-h incubation. Furthermore, adding a large quantity of docetaxel to fenbendazole-treated EMT6 cell cultures greatly reduced their clonogenicity.
This led us to determine whether high doses of fenbendazole might synergize with docetaxel in vivo by increasing the cytotoxic efficacy of docetaxel or by accelerating radiation-induced cell death. Two experiments were performed with this aim. First, tumor-bearing BALB/c mice were randomized to receive either three daily i.p. injections of fenbendazole (50 mg/kg/day) or to be treated with the combination of fenbendazole and 10 Gy of x-rays. Tumor volume measurements were made and compared between groups at various time points. Irradiated tumors grew much slower than unirradiated ones, and this was not affected by the addition of fenbendazole.
The second experiment tested the effect of fenbendazole in combination with docetaxel on the survival of EMT6 tumor cells, using a rigorous colony formation assay. Docetaxel had significant cytotoxic effects against these cells in the absence of fenbendazole. However, adding fenbendazole to the culture greatly enhanced the cytotoxicity of docetaxel, with a dramatic decrease in both the number of surviving cells and the yield-corrected surviving fractions (Figure 3).
The data indicate that fenbendazole acts as a microtubule destabilizer that can disrupt cellular dynamics, thus blocking cell division. It also blocks glucose uptake in cancer cells by blocking insulin-stimulated expression of the GLUT 4 transporter, starving them. This synergy between fenbendazole and docetaxel should be evaluated further in future studies of neoplastic diseases and other conditions whose development might be inhibited by the use of these agents. Moreover, combining fenbendazole with other anti-neoplastic agents could further enhance their effectiveness. fenbendazole for humans