A benzimidazole carbamate drug used to treat parasitic worms has shown promise as an anti-cancer treatment. Researchers found that the drug can stop or slow tumor growth in mice models. It also inhibits the formation of new tumours and reduces the number of cancer cells in the body.
The drug is administered orally every second day for 12 days. It has multiple effects on cancer cells including microtubule polymerization inhibition, glucose uptake blockade, and apoptosis.
Anti-proliferative activity
The anti-parasitic drug fenbendazole can potentially treat some forms of cancer by blocking a tumor’s ability to reproduce, according to researchers at City of Hope. The study, published in the journal Oncotarget on July 6, found that fenbendazole interfered with various cellular pathways to effectively eliminate tumor cells. It caused mitochondrial translocation of p53, inhibited glucose uptake and expression of GLUT transporters, and induced cell death. It also blocked the growth of human xenografts in mouse models.
Fenbendazole (methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl) carbamate) is a broad-spectrum benzimidazole anthelmintic agent that has been used for decades to treat helminth infections in various animal species. It has a moderate microtubule-interfering activity and does not cause significant toxicity in most species tested. It also has a high safety margin, making it an attractive candidate for repurposing as a cancer therapy.
In this study, fenbendazole was administered to mice with pancreatic cancer and examined for its effect on the growth of the tumors. The mice were anesthetized with 100 mg/kg ketamine and 10 mg/kg xylazine before receiving three i.p. injections of fenbendazole in sterile, pyrogen-free physiologic saline.
The results showed that fenbendazole significantly inhibited the growth of pancreatic cancer cells and caused them to undergo apoptosis. The cytotoxic effect of fenbendazole was mediated by its interaction with heparin-binding domains in the microtubules. The results suggest that fenbendazole may be a useful clinical treatment for pancreatic cancer.
Glucose uptake inhibition
Fenbendazole (methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl) carbamate) is an antiparasitic drug that exerts broad-spectrum activity in various animals. It has recently been reported to have antitumor activities mediated by binding to and inhibiting the polymerization of b-tubulin microtubules. It also causes mitochondrial translocation of p53, induces cell cycle arrest in G2/M phase, and blocks glucose uptake by binding to GLUT transporters and hexokinase II. It is also capable of blocking cellular growth in a mouse model.
Unlike conventional chemotherapeutic agents, benzimidazole drugs can be selectively targeted against cancer cells while leaving healthy tissues undamaged. These properties make them attractive candidates for repurposing as anticancer agents. Conventional chemotherapeutics, on the other hand, act non-selectively and can cause adverse effects that negatively impact patients’ quality of life.
To investigate the possible anti-tumor effect of fenbendazole, researchers studied its effect on tumors in genetically engineered mice that develop pancreatic cancer. They found that fenbendazole could slow the development of early-stage pancreatic cancer, as well as inhibit the spread of late-stage disease. The team published its results in Oncotarget on July 6. Gregory Riggins, a professor of neurosurgery and oncology at Johns Hopkins University, led the study with his colleagues Cory Brayton, Tara Williamson, Dimitri G. Trembath, and Thais Biude Mendes. The team also includes researchers from the University of Colorado. The research was funded by the National Institutes of Health and other agencies.
Apoptosis
fenbendazole has a broad spectrum of antihelmintic activity against many species of parasites. It is absorbed by the intestine and converted into its active metabolite, oxifendazole. Oxifendazole is a benzimidazole and has similar microtubule disrupting properties to fenbendazole. In addition to its anthelmintic activities, it has also been shown to have antitumor activity in mice and humans.
Researchers examined the effect of fenbendazole on glucose uptake in cancer cells and found that it inhibited the growth of the cancer cells by blocking the influx of sugar into the cell. This led to a reduction in tumor size and reduced tumor mass in mice that were given fenbendazole. This finding suggests that fenbendazole could be used to treat pancreatic cancer.
Another study found that fenbendazole was able to reduce the proliferation of colorectal cancer (CRC) cells in vitro by inhibiting the signaling pathways involved in cell cycle progression. Moreover, it caused the activation of caspase-3 and PARP, which leads to apoptosis in CRC cells. These results suggest that fenbendazole could provide an effective alternative treatment for CRC patients with resistant to other chemotherapy drugs.
The authors of the study compared the apoptosis-inducing effects of fenbendazole to that of mebendazole, an anti-parasitic drug that was first discovered to have potent anticancer activity in lab experiments in 2002. They found that fenbendazole had more apoptosis-inducing activity than mebendazole in both human colon cancer cells and murine liver cancer cells.
Immunomodulatory activity
Several studies are investigating this class of pharmaceuticals as cancer treatments. However, these are preclinical and have not been tested in humans. The claim that fenbendazole cures advanced lung cancer is controversial and has been dismissed by researchers. It is important to note that fenbendazole is approved as an antiparasitic for dogs, and it has not been shown to be effective in humans. In addition, the drug is not available in a dosage that would be sufficient to treat humans.
Mebendazole, the generic form of fenbendazole, is an anti-parasitic drug that kills parasitic infections by cutting off their supply of nutrition. It does this by targeting tubulin, a protein that functions as the micro-skeleton of the inner cell and a highway for transporting nutrients. The drug also inhibits the formation of tubulin in parasites, causing them to collapse and starve themselves. Researchers believe fenbendazole may act similarly on cancer cells, by collapsing the structure of the cell and preventing it from getting the nutrients it needs.
Researchers treated HL60 leukaemia cells with different concentrations of fenbendazole and observed a mixture of physiological events, including apoptosis and neutrophil differentiation. The apoptosis and differentiation were associated with a reduction in cell numbers and a change in gene expression. The findings suggest that fenbendazole has immunomodulatory activity and could be used to treat leukaemia in combination with other chemotherapy fenbendazole for humans cancer