Fenbendazole (FZ), a member of the benzimidazole family of anthelmintic agents, has a broad antiparasitic range and is also reported to exhibit antitumor effects. Recently, an 80-year-old woman with advanced nonsmall cell lung cancer (NSCLC) self-administered fenbendazole based on social media reports that claimed the drug cures cancer, but 9 months later she experienced severe liver injury. The patient discontinued the self-administration of fenbendazole and her liver dysfunction spontaneously resolved.
The antitumor effect of fenbendazole is thought to be related to its ability to inhibit microtubule-associated tubulin polymerization, which is essential for mitosis. Mitosis is the process of cell division where chromosomes are lined up and separated equally during anaphase, which requires the formation of a structure called the mitotic spindle, which is made of microtubules. Drugs that interfere with the function of microtubules, such as fenbendazole, prevent the formation of the mitotic spindle and block cell division.
A research team at Stanford has been experimenting with fenbendazole, and they found that the drug can suppress tumor growth in mice. This finding is important because it indicates that fenbendazole may have potential as an antitumor drug in humans.
The researchers grew human lymphoma cells in the SCID mice, and then compared their growth when treated with different doses of fenbendazole. They found that a high dose of fenbendazole, which is normally used to treat rodent pinworm infections, significantly reduced tumor growth in the mice. The fenbendazole caused the cells to undergo apoptosis, but not necroptosis. Necroptosis is a form of cell death that is associated with the activation of caspase-8 and cytochrome-C.
To investigate the mechanism of fenbendazole’s antitumor activity, the researchers conducted a series of experiments using various concentrations of the drug. They also tested the effect of a combination of fenbendazole and supplemental vitamins, which is commonly used to treat vitamin deficiencies in laboratory animals. The researchers found that a diet containing fenbendazole and supplementary vitamins significantly decreased tumor growth in the mice, whereas the use of just the fenbendazole alone had no effect.
In addition, the researchers analyzed the behavior of 5-fluorouracil-resistant SNU-C5 cells and found that they did not respond to fenbendazole treatment in the same way as wild-type cells. The fenbendazole-resistant cells exhibited reduced autophagy and ferroptosis, and had less activation of p53 and caspase-8. The findings suggest that a combination of fenbendazole with other treatments, such as 5-fluorouracil and methotrexate, could be a good therapy for cancer patients that develop resistance to these drugs. The results also indicate that the mechanisms by which fenbendazole blocks tumor growth in 5-fluorouracil-resistant cells need further study, but they are encouraging because they may help to design new therapeutic strategies for treating fenbendazole for cancer