Developing new drugs takes years, and it can cost millions. But a deworming drug that was originally developed to treat parasites in dogs appears to have surprising anti-cancer properties. Fenbendazole (FZ) has been shown to kill cancer cells in animal research. But fenbendazole hasn’t gone through clinical trials to find out whether it can help human patients. And while it is safe to take, it can interact with other medications and supplements, causing side effects or reducing its effectiveness.
The anthelmintic drug fenbendazole (Memethyl 5-(phenylsulfanyl)-1H-benzimidazo-2-yl) carbamate is able to inhibit tubulin polymerization and prevent the formation of microtubules in the cell. It has recently been repurposed to overcome cancer resistance. For example, a study showed that fenbendazole significantly decreased tumor size in female athymic nu/nu mice when administered orally. It also suppressed RAS-related signaling pathway expression in lung cancer cells with a KRAS mutation, suggesting that fenbendazole may be a novel anticancer agent with a different mechanism of action than conventional cancer drugs.
To determine the underlying mechanisms of fenbendazole’s anti-cancer activity, we studied fenbendazole’s effect on cell viability and apoptosis in wild-type and 5-fluorouracil resistant SNU-C5 colorectal cancer cells. We found that fenbendazole reduced the viability of both the wild-type and 5-fluorouracil-resistant cells, as well as suppressed the G2/M phase progression of the latter. Moreover, we demonstrated that fenbendazole induces ferroptosis in the former and augments apoptosis in caspase-8-dependent manner without affecting p53 activation. Further, we uncovered that GPX4 is the key enzyme responsible for ferroptosis-augmented apoptosis. fenbendazole cancer treatment