Fenbendazole is a common drug used as an antiparasitic agent in many animal species to treat pinworms, roundworms, hookworms, giardiasis, and Taenia solium. Previously, it has been reported that anthelmintics (drugs used to treat parasites) can have anticancer effects as well. However, it is challenging to move from preclinical evidence to a proven treatment. The journey from an anthelmintic to a clinically approved drug can take up to 25 years.
The researchers analyzed the effect of fenbendazole on 5-fluorouracil-resistant colorectal cancer cells. They found that fenbendazole inhibited the proliferation of both wild-type and 5-fluorouracil-resistant SNU-C5 cells. Treatment with fenbendazole also induced cell death through apoptosis, autophagy, ferroptosis, and necroptosis.
Benzimidazole binding to tubulin disrupts microtubules, which are polymers that form part of the cell’s cytoskeleton and provide structure and shape to the cell. Tubulin is also a highway for transporting nutrients to and from the cell’s interior. Inhibiting tubulin’s formation starves the cancer cells by cutting off their supply of nutrients and causes them to collapse.
The scientists further discovered that fenbendazole can cause apoptosis and cell cycle arrest through p53 and p21 pathways in 5-fluorouracil-resistant SNU-C5 cancer cells. In addition, they found that fenbendazole induces necroptosis in 5-fluorouracil-resistant colorectal tumor cells. The researchers showed that fenbendazole increased the expression of necroptosis-related proteins, including RIP, pMLKL, and caspase-8, while decreasing phosphorylation of ERK in both wild-type and 5-fluorouracil-resistant colorectal cell lines. They also demonstrated that GPX4 plays an important role in fenbendazole-induced necroptosis.fenbendazole for humans cancer