Fenbendazole: An Overview

What is Fenbendazole and How Was It Created?

Fenbendazole is a broad-spectrum anthelmintic drug developed in the 1970s by Hoechst AG, a German pharmaceutical company (now part of Sanofi). Introduced as a veterinary antiparasitic in 1974, it was designed to combat gastrointestinal parasites in animals like dogs, cats, horses, and livestock. Its creation stemmed from research into benzimidazole compounds, which showed promise in disrupting parasite metabolism, leading to its widespread use in animal health.

Effects on Cancer Cells and Tumors

Fenbendazole has gained attention for its potential anticancer properties, observed in preclinical studies. It appears to inhibit cancer cell growth and induce cell death, while also showing effects on tumor size and progression in animal models. These effects are not fully validated in human clinical trials but have sparked interest in repurposing the drug.

Potential Uses of Fenbendazole

• Treating Parasitic Infections: Fenbendazole eliminates parasites like roundworms, hookworms, and tapeworms in animals.
• Inhibiting Cancer Cell Growth: It may slow or stop cancer cell proliferation in lab settings.
• Inducing Apoptosis in Cancer Cells: Triggers programmed cell death in malignant cells.
• Reducing Tumor Size: Shown to shrink tumors in some animal studies.
• Enhancing Chemotherapy Effects: May boost the efficacy of drugs like docetaxel in preclinical models.

Cancers Potentially Targeted by Fenbendazole

Based on preclinical research, fenbendazole has shown potential effects against the following cancers. Note that these findings are preliminary and lack confirmation from human clinical trials:

• Colorectal cancer
• Non-small cell lung cancer
• Lymphoma
• Pancreatic cancer
• Prostate cancer
• Breast cancer
• Glioblastoma
• Melanoma
• Leukemia
• Hepatocellular carcinoma

Mechanisms of Action

Treating Parasitic Infections

Fenbendazole binds to tubulin in parasite cells, disrupting microtubule formation. This prevents nutrient absorption, starving the parasites and causing their death. It’s effective against both adult and larval stages, making it a staple in veterinary medicine.

Inhibiting Cancer Cell Growth

In cancer cells, fenbendazole acts as a moderate microtubule destabilizer. By binding to tubulin, it disrupts the mitotic spindle during cell division, halting proliferation. Studies show it affects human cancer cell lines at micromolar concentrations, slowing growth significantly.

Inducing Apoptosis in Cancer Cells

Fenbendazole triggers apoptosis by activating the p53-p21 pathway, increasing p53 expression in some cancer cells (e.g., colorectal cancer). This leads to mitochondrial damage and caspase-mediated cell death, effectively eliminating malignant cells while sparing normal ones in preclinical tests.

Reducing Tumor Size

In animal models like mice with mammary tumors, fenbendazole has reduced tumor volume, possibly by starving cancer cells of glucose. It downregulates GLUT transporters and hexokinase II, key players in cancer metabolism, leading to tumor regression in some cases.

Enhancing Chemotherapy Effects

When combined with drugs like docetaxel, fenbendazole shows additive cytotoxicity in vitro. It doesn’t alter the dose-response of chemotherapy but enhances cell death by compounding microtubule disruption, suggesting potential as an adjuvant therapy in experimental settings.