Anti-Tumor Activity of Fenben

The benzimidazole compound fenben, also known as Panacur, is used extensively to treat parasitic infections in animals, especially lungworms and gastrointestinal nematodes. Recently, it has been shown to display potent anti-tumor activity in animal models and in human cancer xenografts. The drug inhibits cell growth by interfering with microtubule assembly and mitotic spindle formation. It has also been found to interact with cyclin B1 and to bind to the colchicine binding site of tubulin in vitro, and it blocks phosphorylation and activation of hexokinase, a glycolytic enzyme required for cell-cycle progression, in A549 cells.

The effect of graded doses of fenbendazole on the viability of EMT6 cells in culture was assessed by a colony formation assay, and survival data were plotted with rigorous error bars using yield-corrected surviving fractions. 2-h treatments of fenbendazole did not affect cell numbers in monolayer cultures, whereas 24-h incubation with high doses reduced clonogenicity and cell number. Severe hypoxia significantly increased the toxicity of 2-h treatments, which was consistent with previous findings in other cells.

We next investigated whether fenbendazole interfered with the microtubule network by treating A549 cells with 1 uM FZ for different time intervals. The results indicate that FZ rapidly binds to tubulin and alters its polymerization status, whereas it has no effect on the accumulation of the polymerized cyclin B1. Moreover, treatment with a high concentration of FZ for 24 h induces a mitotic catastrophe in A549 cells. In vivo, we transplanted sarcoma cells into athymic nu/nu mice and found that orally administered fenbendazole suppressed tumor growth in a mouse model with a KRAS mutation.