Fenbendazole is an antiparasitic drug used to treat parasitic infections, including hookworms, whipworms, tapeworms, and other parasitic worms. It has also been used to treat certain types of cancer, and is currently being studied in clinical trials for the treatment of a number of other diseases. Recently, it has become popular among cancer patients after a man named Joe Tippens claimed that it cured his lung cancer. However, the claim was largely based on the fact that he had been taking a combination of fenbendazole and a number of other supplements.
Researchers have now discovered that fenbendazole causes tumour cell death in part by disrupting the microtubule network. They did this by treating human non-small cell lung cancer cells with fenbendazole and analysing them using immunofluorescence. They found that the drug partially alters the microtubule network around the nucleus of cancer cells, which leads to their apoptosis. In addition, they found that fenbendazole has a greater effect in cells with wild type p53 genes than mutant ones.
The researchers then looked at the effects of fenbendazole on 5-FU-sensitive SNU-C5 and 5-FU resistant SNU-C5/5-FUR colorectal cancer cells. They found that fenbendazole induces time-dependent G2/M arrest and apoptosis in both CRC cell lines. They also found that fenbendazole activates apoptosis via p53-p21 pathways in the sensitive cells, while it promotes apoptosis and ferroptosis through a different mechanism in the resistant cells.
Using an MTT assay, the researchers found that fenbendazole inhibited the growth of both cancer cells at micromolar concentrations. In addition, they tested whether fenbendazole caused mitochondrial injury or caspase-3-PARP activation in both cells. They found that fenbendazole significantly inhibited the proliferation of both cells by activating mitochondrial apoptosis in SNU-C5 cells, and by enhancing p53-independent apoptosis and ferroptosis in the resistant cells.
They also determined that fenbendazole inhibited glucose uptake in both SNU-C5 and SNU-C5/5-FUR cells. This led them to conclude that fenbendazole has the potential to be a therapeutic agent against 5-FU-resistant CRC.
To further explore the anti-cancer mechanisms of fenbendazole, they treated both cell lines with fenbendazole and compared them to control cells that were treated with either a low or high concentration of the drug. They found that fenbendazole caused an increase in free iron by decreasing the expression of cysteine uptake proteins SLC7A11 and GPX4. This led to the accumulation of free iron and subsequent induction of ferroptosis. They also observed that fenbendazole significantly increased the levels of necroptosis-related proteins, including phospho-receptor-interacting protein kinase (pRIP), RIP3, phospho-mixed lineage kinase domain-like protein 1 (MLKL), and caspase-8 in both cells. They also found that fenbendazole-induced necroptosis involves lipid peroxidation, which is linked to GPX4 activation and apoptosis. The authors concluded that these results suggest that fenbendazole induces tumor cell death through both autophagy and ferroptosis in 5-FU-sensitive CRC cells, and apoptosis and ferroptosis as main pathways in the 5-FU-resistant cells. They speculated that this might explain why fenbendazole is more effective in the 5-FU-resistant cells. The authors also indicated that they were investigating the effects of a combination of fenbendazole with other compounds that may have synergistic effects, such as the pyrimidine analogues doxorubicin and deferoxamine mesylate. fenbendazole cancer