Fenbendazole is an animal anthelmintic that is used at low doses for a number of parasitic infections in humans. It has also been shown to have anti-cancer effects in lab experiments. In this study, fenbendazole was shown to be effective against both 5-FU sensitive and resistant colorectal cancer (CRC) cells. It is believed to work by activating both p53-dependent and -independent pathways of cell death. In addition, the drug is found to increase both apoptosis and ferroptosis in these cells.
Cells were incubated for 2 h with fenbendazole at concentrations that are well below the limit of solubility and analyzed for changes in the numbers of viable cells using a clonogenic assay. Cells treated under hypoxia exhibited greater sensitivity to the drug as evidenced by a steep decrease in cell numbers and an increased apoptotic index. These changes are attributed to the inhibition of tubulin polymerization.
Inhibition of tubulin polymerization is known to block cell-cycle progression by inhibiting the activity of cyclin B1, which is required for cell division and must be degraded by the anaphase-promoting complex in order for mitosis to occur. The concentration of cyclin B1 is rapidly elevated in FZ treated cells and the cell cycle is disrupted through anaphase catastrophe.
To test whether fenbendazole acts as a radiosensitizer, the EMT6 tumor-bearing mice in the BALB/cRw model were randomly assigned to receive three daily i.p. injections of either fenbendazole or placebo. The appearance and behavior of the mice were monitored throughout the experiment, and their weights measured at necropsy at the time indicated by each point on the graph. Mice that received fenbendazole showed a significant reduction in tumor growth and in the number of spontaneous lung metastases. fenbendazole for cancer