Fenbendazole Stage 4 Colorectal Cancer

Fenbendazole (FZ) is a moderate microtubule destabilizer that induces cancer cell death by modulating multiple cellular pathways. It causes apoptosis and cell cycle arrest at G2/M phase in both 5-fluorouracil sensitive and resistant colorectal cancer cells. However, the mechanism by which it exerts these anti-cancer effects remains unclear. We analyzed the effect of FZ on various cell death pathways using MTT assay, Western blotting and flow cytometry assays. We found that FZ induced both p53-dependent apoptosis and ferroptosis-augmented apoptosis in CRC cells. It also augmented necroptosis triggered by mitochondrial injury and decreased expression of GPX4 leading to lipid peroxidation. Treatment with ferrostatin-1 and DFOM, which inhibit SLC7A11-dependent ferroptosis and necroptosis respectively, did not prevent the anti-cancer effects of FZ in both SNU-C5 and SNU-C5/5-FUR cells. This suggests that benzimidazole-induced cell death is not mainly through ferroptosis and necroptosis but rather through a combination of apoptosis, autophagy and ferroptosis mediated by DAMPs.

Benzimidazole interferes with glucose uptake in cancer cells and blocks the production of ATP by inhibiting expression of GLUT transporters and hexokinase II. This decreases ATP levels and leads to cell energy deprivation triggering various stress responses including cell death. fenbendazole stage 4 cancer

Leave a Reply

Your email address will not be published. Required fields are marked *