Fenbendazole is an animal anthelmintic used to treat gastrointestinal helminths such as flukes, lungworms and tapeworms. It is also given to dogs and cats for a number of parasitic intestinal infections including Giardia. The benzimidazole binds to tubulin and disrupts its microtubule equilibrium, causing a loss of stability. It also inhibits cell growth by affecting the synthesis of protein and lipids. In human cancer cells, fenbendazole has been shown to inhibit glucose uptake, an essential nutrient for tumours.
Researchers studied the effect of fenbendazole on H460 and A549 cancer cell lines and found that fenbendazole reduces cellular energy by blocking glycolysis, leading to a loss of ATP and subsequent arrest of the cell cycle. It also reduces phosphorylation of key protein targets involved in regulating cell cycle progression and DNA damage repair. In addition, fenbendazole inhibited the ability of tumour cells to evade chemotherapy through upregulation of p53 and downregulation of the G2/M checkpoint regulator p21.
The researchers then tested the effect of fenbendazole in combination with taxanes. They injected BALB/c mice with EMT6 tumors and randomly assigned them to groups that received three daily i.p. injections of fenbendazole, 10 Gy of radiation alone or a combination of the two drugs. They found that the growth of unirradiated tumors was not affected by fenbendazole alone, but that its effects were enhanced when it was given prior to irradiation (Figure 3).
Treatment with fenbendazole reduced clonogenicity in both radiation-treated and -untreated cells, suggesting that it interfered with taxane-induced cell death. They observed that irradiation of cells treated with fenbendazole prior to radiation led to a greater increase in the yield-corrected percentage of surviving cells, which was associated with increased autophagy and ferroptosis. This suggests that fenbendazole, via its benzimidazole group, may be able to enhance the efficacy of some chemotherapy agents. fenbendazole for humans