Mebendazole (MZ) (methyl 5-benzoyl-2-benzimidazole-carbamate) is a broad-spectrum anthelmintic (antiworm) drug. It is used to inhibit the growth and multiplication of newly hatched insects in your body. It promotes the depolymerization of tubulin and destroys the function of microtubules in insects. Benzimidazole has two derivatives MZ and albendazole. MZ has anticancer activity. It causes mitotic arrest in cancerous cells that leads to cell death. It is very effective against lung cancer.
Non-small cell lung cancer
Lung cancer is one of the leading causes of death all over the world. Non-small cell lung cancer (NSCLC) is very common kind (85%) of lung cancer in smokers and non-smokers. It is more common in females than in males. NSCLCs have a very poor prognosis and such patients are less sensitive to chemotherapy as compared to small cell carcinoma.
Mechanism of Action
Scientific studies have shown that MZ prevents the normal spindle formation in NSCLC by inhibiting the polymerization of tubulin. This abnormal spindle formation causes mitotic arrest at prometaphase of cell division and ultimately leads to cell death. Mebendazole also induces phosphorylation and produces changes in the expression of cell cycle regulatory proteins that are also associated with the mitotic arrest.
After the mitotic arrest in cancer cells, Mebendazole initiates apoptosis (cell death) in NSCLC cells. However, this mechanism is not entirely understood. Chemotherapeutic agent paclitaxel acts on these cancerous cells just like MZ by more than one pathway, induces the destruction of mitochondria and causes apoptosis. It causes phosphorylation of certain proteins such as Bcl-xl or Bcl-2 and damages the microtubules of the cell. Studies claimed that this phosphorylated protein Bcl-xl or Bcl-2 causes increased Bax level. This condition favors cell apoptosis.
In vitro MZ treatment
In vitro treatment, MZ prevents the growth of NSCLC cell lines. Only 0.1 µM dose of MZ can suppress the proliferation of cells significantly. A dose of 10 µM suppresses the 75% of cell lines. The standard dose is 0.5 µM for in vitro experiments. In NSCLC cell lines, A549 cells are the least sensitive cells to MZ and H460 cells are the most sensitive cells to Mebendazole. It causes condensation and destruction of the nuclear membrane that leads to mitotic arrest of dividing cancer cells.
Researches show that when in vitro apoptosis was induced by MZ Treatment, after 24 hours, sub-diploid cells increased significantly. The level of cells increases with the duration of treatment. It suggests that Mebendazole promotes cell death after the mitotic arrest. MZ induce mitochondria to secrete of cytochrome c to the cytosol of the cell.
Proper spindle formation is essential for the normal division of cells. Mebendazole treatment induces abnormal spindle formation in tumor cells. When such cells are treated with Mebendazole, paclitaxel (a chemotherapeutic drug), nocodazole (antineoplastic agent) or DMSO (dietary supplement), they target tubulin polymerization and its status varies with different chemical agents.
In Vivo Tumor Suppression
In scientific research, cells of mice were treated in vivo by Mebendazole with varying doses, it was found that cells receiving 1-mg MZ dose, showed growth inhibition effect remarkably. Numerous experiments showed that MZ treatment is more effective than other chemotherapeutic agents in suppressing cell growth.
Effect of MZ on s.c. Tumor Growth
The anti-cancerous effects of MZ were experimented on H460 xenografts in mice. When tumor cells attained a diameter of 5 mm, a dose of 1mg was given through the oral route. After a treatment period of 7 days, tumor cells showed significant suppression and apoptosis. The following figure shows the remarkable effectiveness of MZ treatment on the tumor cells.
Vitamins + fenbendazole
Scientific studies claim that a combination of vitamins and Fenbendazole is effective in suppressing human lymphoma cells. But when we treat the tumor with only fenbendazole, it has no inhibitory effects on tumor cells. Vitamins D, K, A, B, E are supplemented. Vitamins A and E possess antioxidant properties, so they are effective against tumor cells. They inhibit the nuclear transcription factor.
Mebendazole is a famous antiparasitic drug and it has significant activity in microtubule and fibroblast inhibition and suppresses the tumor cells remarkably. No side effects have been reported so far. But when MZ is used to treat alveolar echinococcosis (a parasitic disorder) for the long term, it shows a little bit of tolerable toxicity. But when these cancerous cells are treated with other anthelmintic agents like albendazole, neutropenia is reported. MZ is a useful chemotherapeutic agent and can be used in lung cancer therapy. But when MZ is compared with other chemotherapeutic agents like nocodazole, it is less efficient in depolymerization of tubulin and inducing abnormal spindle formation and in cancerous cells.