A Stanford virologist did not set out to battle cancer, but his efforts to thwart viruses that cause diseases like hepatitis and the common cold may have led to a new collaboration and a promising drug. In a paper published in the journal Nature, Jeffrey Glenn, MD, and colleagues report that fenbendazole (FZ), a benzimidazole anthelmintic agent commonly used to treat parasitic infections, appears to effectively kill colorectal cancer cells in mice and to enhance the effectiveness of other treatments such as radiation or chemotherapy.
The benzimidazole family of drugs are known to bind beta-tubulin, disrupt microtubules and inhibit cell division. They also have been shown to elicit mitotic catastrophe and apoptosis through the activation of JNK and p53 in HCT116 and SW480 cells . Several benzimidazole compounds including mebendazole, albendazole, and praziquantel exhibit anti-tumor activity in CRC patients with advanced disease and are being explored as potential alternative or supplementary therapies.
However, a recent video by an unlicensed veterinarian who promoted a dog deworming medicine as a cure for human cancer has garnered significant attention on social media, with many people who have cancer claiming to have been healed from self-administration of fenbendazole based on accounts posted on TikTok and Facebook. The McMaster University team is working to determine whether the claims of healing are based on actual science and to explore the mechanisms by which fenbendazole might work as a cancer therapy.
To study the anti-cancer effects of fenbendazole, a cell viability assay with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and JC-1 (5,5′,6,6′-tetrachloro-1′,1′,3,3′-tetraethyl benzimidazoleocarbocyanine iodide) was performed in SNU-C5 and SNU-C5/5-FUR cells that had been treated with various concentrations of fenbendazole. To identify the underlying mechanisms, we also measured autophagy, ferroptosis and necroptosis in these cells.
In fenbendazole-treated cells, apoptosis was augmented by JC-1 induction and increased mitochondrial injury markers such as cytochrome-C. In addition, fenbendazole enhanced autophagy, mitotic catastrophe and ferroptosis in 5-FU resistant cells. Ferroptosis was augmented in the presence of DFOM, which is an iron chelator to block SLC7A11-dependent ferroptosis, but not in the presence of a p53 inhibitor such as PD184352, suggesting that p53 is not required for fenbendazole-induced cell death.
In contrast, fenbendazole enhances the cytotoxicity of radiation or chemotherapy drugs in these resistant cells and reduces multidrug resistance by blocking the binding of doxorubicin to its target protein MDM2. We have identified that fenbendazole elicits this effect by targeting the ubiquitin-like domain of MDM2. Thus, our results show that fenbendazole could be a novel therapeutic approach for treating chemoresistant CRC. MTT, JC-1, Hoechst 33342, propidium iodide, horseradish peroxidase conjugated anti-mouse IgGs and FITC anti-rabbit IgGs, DFOM, ferrostatin-1, DPOM and TRI reagent were purchased from Sigma. fenbendazole for cancer