Mebendazole: An Overview

What is Mebendazole and How Was It Created?

Mebendazole, a benzimidazole antiparasitic drug, was developed in 1971 by Janssen Pharmaceutica in Belgium. Initially introduced as a veterinary anthelmintic, it was later approved for human use to treat parasitic worm infestations such as pinworm, roundworm, and hookworm. Its broad-spectrum efficacy made it a cornerstone of global parasite control, earning a place on the World Health Organization's List of Essential Medicines.

Effects on Cancer Cells and Tumors

Preclinical studies suggest mebendazole inhibits cancer cell growth, migration, and metastasis while inducing apoptosis and disrupting tumor angiogenesis. In animal models, it has shown potential to reduce tumor size and prevent metastasis, though robust human clinical data is still lacking.

Potential Uses of Mebendazole

• Treating Parasitic Infections: Effectively targets intestinal nematodes like pinworm, whipworm, and hookworm in humans and animals.
• Inhibiting Tumor Growth: Suppresses proliferation of cancer cells in lab and animal studies across multiple cancer types.
• Inducing Cell Death: Triggers apoptosis and autophagy in cancer cells via microtubule disruption and other pathways.
• Overcoming Drug Resistance: May enhance chemotherapy sensitivity in resistant cancer cells by inhibiting efflux pumps.

Cancers Potentially Targeted by Mebendazole

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

• Colorectal cancer
• Ovarian cancer
• Glioblastoma
• Lung cancer (non-small cell)
• Adrenocortical carcinoma
• Breast cancer
• Melanoma
• Pancreatic cancer
• Leukemia
• Prostate cancer

Mechanisms of Action

Treating Parasitic Infections

Mebendazole binds to the colchicine-sensitive site of β-tubulin in parasites, inhibiting microtubule polymerization. This disrupts glucose uptake and cellular transport, leading to parasite immobilization and death, particularly effective against nematodes.

Inhibiting Tumor Growth

In cancer cells, mebendazole disrupts microtubule dynamics, arresting the cell cycle at the G2/M phase. It also inhibits key oncogenic pathways such as Hedgehog, Wnt/β-catenin, and NF-κB, slowing tumor proliferation in preclinical models.

Inducing Cell Death

Mebendazole promotes apoptosis by depolarizing mitochondrial membranes and releasing cytochrome c, alongside increasing reactive oxygen species (ROS) levels. It also induces autophagy, contributing to cancer cell death in vitro.

Overcoming Drug Resistance

By inhibiting P-glycoprotein efflux pumps, mebendazole reduces multidrug resistance in cancer cells. It may also modulate the tumor microenvironment, enhancing immune responses and sensitizing tumors to conventional therapies in experimental studies.