Can Fenbendazole Treat Colorectal Cancer?
The antiparasitic medication fenbendazole has recently been linked to cancer treatment, with a 2018 study by Scientific Reports showing that the drug could block proliferation of cancer cells and promote cell death in laboratory culture (in vitro). The nonprofit organization Cancer Research UK told PolitiFact that “there is insufficient evidence at this time to support Tippens’ claim that fenbendazole can cure cancer,” and that the claims haven’t gone through any clinical trials to determine whether they are true.
The commercially available anthelmintic drug fenbendazole displays anti-tumor activities in human colorectal cancer cells. However, the exact mechanism of fenbendazole’s cytotoxic effect remains unknown. Single-target drugs may show limited efficacy in cellular processes and have the tendency to develop resistance, so it is desirable to design agents that target multiple cellular targets for more effective treatment.
Previous studies showed that fenbendazole enhanced the sensitivity of 5-fluorouracil-resistant CRC cells to radiation and docetaxel by both enhancing p53-independent apoptosis and promoting ferroptosis-augmented apoptosis. Therefore, we investigated the effects of fenbendazole in 5-fluorouracil-resistant SNU-C5 and SNU-C5/5-FUR cells to identify its anti-cancer mechanisms.
We found that fenbendazole significantly suppressed the proliferation of both SNU-C5 and SNU-C5/5-FUR in a dose-dependent manner. The fenbendazole-induced decrease in cell viability was largely caused by the inhibition of free iron levels through the reduction of cysteine uptake by SLC7A11 or the inactivation of the GPX4 lipid repair enzyme. The treatment of SNU-C5 cells with ferrostatin-1 or deferoxamine mesylate (DFOM) to inhibit ferroptosis did not prevent fenbendazole’s anti-proliferative effects, suggesting that ferroptosis is the main pathway by which fenbendazole induces anti-tumor activity in 5-fluorouracil-resistant CRCs. fenbendazole cancer