Fenbendazole is a dewormer that was found to also kill cancer cells. It blocks the cells ability to metabolize sugar and boosts production of p53, which keeps cancer cells in check.
Using a clonogenic assay, it was found that both free FEN and RAPA significantly inhibited colony formation at all concentrations tested. This finding was attributed to FZ’s moderate microtubule targeting activity causing mitotic arrest and cancer cell death.
What is Fenbendazole (FZ)?
Fenbendazole (FZ) is an anthelminthic drug that is used to treat parasitic worms such as ascarids, whipworms, hookworms, and a single species of tapeworm in animals like dogs, cats, pigs, and horses. This pleiotropic benzimidazole carbamate group drug displays anti-neoplastic activity and is a promising candidate for repurposing as an anticancer agent.
FZ interferes with microtubule dynamics in cancer cells by affecting a variety of cellular processes including cell cycle progression, induction of apoptosis, autophagy and interfering with glycolysis (Fig. 9a). These pleiotropic effects and the ability to evade drug resistance make FZ a potential antineoplastic agent.
Treatment of human non-small cell lung cancer (NSCLC) cells with FZ resulted in an arrest in the progression of the cell cycle and induction of apoptosis. This was accompanied by a reduction in anchorage-independent growth and Hoechst 33342 staining of apoptotic nuclei, as shown in Fig. 9b,c. Moreover, a decrease in glucose uptake and expression of the GLUT transporters as well as hexokinase II was observed in H460 cells treated with FZ.
How does FZ work?
FZ is a type of medication that works by blocking certain proteins from being released in the body. This helps prevent cancer cells from growing and spreading. FZ is also used to treat genitourinary tract cancers like testicular cancer and prostate cancer. FZ can be used alone or with other medications to treat these cancers.
Fenbendazole is an animal anthelmintic with only limited experience in humans (Ann Trop Med Parasitol 1976;70(2):205-11. Effectiveness of single doses of fenbendazole Hoe 88I against Ascaris, hookworm and Trichuris in man). It has been shown to have potent anti-cancer activity in lab experiments.
The FZ genotype is an AATD genotype, which increases the risk for obstructive lung disease and liver disease. Individuals with this genotype may be referred to a physician familiar with Alpha-1 antitrypsin deficiency for personalized screening and management recommendations.
What is the FZ drug dosage?
FZ causes mitotic arrest and cell death in cancer cells and suppresses tumorigenesis. It also inhibits glucose uptake in cells by down regulation of GLUT transporters and hexokinase, which is a key glycolytic enzyme. Furthermore, p53 is translocated to mitochondria and is activated by FZ. This potent combination of multiple cellular pathways results in effective elimination of tumour cells in vitro and in vivo.
To investigate the effect of FZ on the organization of mammalian microtubules, human non-small cell lung carcinoma (NSCLC) cells were treated with 1 uM FZ for 24 h and stained with anti-tubulin antibodies. Unlike colchicine treatment, which induces complete depolymerization of microtubules into tubulin subunits, FZ only caused a partial distortion of the underlying microtubule network.
In addition, we showed that the tumor growth inhibitory effects of FZ can be enhanced by combining it with the microtubule targeting agent taxol, the glycolytic inhibitor 2 deoxyglucose (2DG), or dichloroacetate (DCA) – a pyruvate dehydrogenase kinase inhibitor that shifts metabolism towards glucose oxidation. Furthermore, it was found that the tumor growth inhibitory effects of FZ are independent of P-gp.fenben cancer treatment