Fenbendazole is a broad-spectrum benzimidazole anthelminthic approved for use in numerous animal species. It’s also a moderate microtubule destabilizer and causes cancer cell death through two distinct pathways.
Cellular structures and shape are established by a protein scaffold known as the cytoskeleton. Tubulin is one component of this structure and fenbendazole interferes with its formation.
Antiparasitic
Fenbendazole is an antihelmintic medication commonly used in broiler chickens and replacement chickens intended to become breeding stock, for the treatment and control of adult Ascaridia galli. It is also used in nonlactating goats, and a wide variety of other animals including horses, cattle, pigs, sheep, and birds. It is also used to remove stomach worms in dogs and cats, as well as big cats (eg, lions, leopards, tigers).
The antiparasitic properties of fenbendazole result from its ability to interfere with the formation of microtubules, an important structural component of cells. Cells establish their shape and structure through a highly dynamic protein scaffold called the cytoskeleton, which contains microtubules.
The ability of fenbendazole to destabilize microtubules causes tumor cells to die by inhibiting the cell cycle, which is required for cell replication. In a colony formation assay, high doses of fenbendazole significantly reduced the clonogenicity of EMT6 tumors in vitro. Similar results were obtained in a mouse model, where three daily i.p. injections of fenbendazole were shown to reduce the growth of EMT6 mammary carcinomas in mice.
Antimicrobial
Fenbendazole is an anthelmintic and has been found effective against parasites in laboratory animals. It is also an antimicrobial and shows promising activity against cryptococcal infections in humans, which are associated with high mortality rates and whose treatment is often expensive and toxic.
The antifungal properties of fenbendazole are due to its binding to b-tubulin and blocking microtubule polymerization. Microtubules are important for cell growth and are involved in the separation of chromosomes during mitosis. Drugs that interfere with microtubules prevent these processes from occurring, and they are commonly used as cytotoxic anticancer agents.
Fenbendazole is not absorbed into the bloodstream and has low toxicity in a wide range of animals. It is not toxic to pigs, dogs, cats, horses or cattle and is well tolerated in rabbits and mice. It should not be given to pet poultry that are growing new feathers or during molting, as it may inhibit their development. It should not be administered in conjunction with bromsalan flukicides (eg, dibromsalan and tribromsalan), as they are known to cause abortions in cattle and death in sheep.
Antioxidant
Fenbendazole (methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl) carbamate), a broad-spectrum benzimidazole anthelmintic, is widely used in animal species. It has a high margin of safety and is well tolerated. Repurposing of veterinary drugs that show promise for human use is an important strategy to reduce development time and cost.
We used the EMT6 mammary tumor cell line in vitro and solid tumors in mice to evaluate cytotoxic and antitumor properties of fenbendazole. We also investigated its potential in combination with hypoxia-selective nitroheterocyclic cytotoxins/radiosensitizers, taxanes, and the COX-2 inhibitors.
Treatment with fenbendazole resulted in reduced clonogenicity of the cells, and these effects increased with the duration of exposure. Furthermore, fenbendazole significantly decreased the numbers of cells in the cultures after a 24-h incubation. This reduction was quantified by using a yield-corrected colony formation assay.
We conclude that fenbendazole has antioxidant properties and can protect against tumorigenesis by reducing oxidative stress. It does not, however, increase the antineoplastic effects of radiation or docetaxel. In addition, fenbendazole did not significantly enhance the cytotoxicity of rapamycin, due to its low solubility. These findings suggest that further testing is warranted.
Anti-inflammatory
Fenbendazole (methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl) carbamate) is a broad-spectrum benzimidazole anthelmintic used in several animal species to control parasites. Repurposing veterinary drugs with promising results for human uses reduces the time and cost of drug development and provides access to safe and effective therapeutic agents that would otherwise not be available.
Cells establish shape and structure through a protein scaffold called the cytoskeleton, which is composed of structures called microtubules. Textbook depictions of cells resemble amorphous bags of liquid, but in truth, cells are highly dynamic and are constantly assembling and disassembling cytoskeleton components to meet the demands of their environment.
Mebendazole interferes with the formation of microtubules by binding to a component of them called -tubulin. This binding disrupts the assembly and disassembly of cytoskeleton components, which leads to a loss of cell stability and apoptosis. Hypoxia increases the toxicity of fenbendazole, and survival curves for cultured tumor cells treated with it show a steep decrease in viability at low doses followed by a plateau of constant cell numbers at higher fenbendazole concentrations (Fig. 1). fenben lab fenbendazol
0 Comments