Fenbendazole Stage 4 Colorectal Cancer
Fenbendazole (methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl) carbamate) is an antiparasitic agent used for the treatment of various gastrointestinal parasites such as pinworms, giardia, roundworms, hookworms, and Taenia solium. It is also widely used to treat pulmonary paragonimiasis in animals. In recent years, it has been repurposed as an anticancer drug due to its wide clinical use in humans and its effectiveness in overcoming cancer resistance to conventional chemotherapy.
We have previously shown that fenbendazole induces apoptosis and cell cycle arrest in 5-FU-sensitive and resistant colorectal cancer cells. However, the mechanism by which fenbendazole induces cell death is not well understood. In this study, we evaluated the effect of fenbendazole on the expression of autophagy proteins including Beclin-1 and LC3-I in both 5-FU-sensitive and resistant SNU-C5 colorectal cancer cells. Western blot results showed that fenbendazole induces the expression of these proteins in both cell types. In addition, we demonstrated that fenbendazole induces both p53-independent apoptosis and ferroptosis-augmented apoptosis in 5-FU-resistant SNU-C5 cells.
We suggest that fenbendazole exerts its anticancer effects by the inhibition of tubulin polymerization. Tubulin polymers make up microtubules, which are part of the cytoskeleton that provides structure and shape to the cell. This action is similar to the cytotoxic effects of vinca alkaloids and taxanes. Inhibition of the cell cycle by fenbendazole may be associated with mitotic catastrophe and its effect on cyclin B1 is likely to be mediated via ubiquitin-proteasome-dependent degradation of CDK1. Furthermore, our data indicate that fenbendazole enhances apoptosis and reduces tumor growth in 5-FU-resistant CRC cells.fenbendazole stage 4 cancer