Fenbendazole is an anthelmintic drug used to treat parasitic worms in humans and animals. It has a broad spectrum and is effective against multiple types of parasitic worms.
It also suppresses the growth of cancer cells. It does this by preventing the formation of microtubules that support the structure of cancer cells.
Microtubules are a dynamic component of cytoskeleton and are essential for cell division, mitosis, cellular migration, and cell structure. They can be stabilized by the antineoplastic agents taxanes and epothilones through their binding to tubulin1,2. The primary mechanism of action for these drugs is suppression of microtubule growth by destabilizing the microtubule-tubulin complex3.
These drugs have been developed as antihelminthic and anticancer agents and are effective against many solid tumors. However, they exhibit a range of side effects and resistance is common. A novel, microtubule-targeting compound – SPC-160002 (SPC-1600) – shows promise as a potent anticancer agent. It suppresses the clonogenicity of tumor cells by inhibiting tubulin polymerization, and its antineoplastic activity is enhanced when combined with other drugs, including taxanes.
To evaluate the long-term anticancer effects of fenbendazole, we used an established clonogenic assay in HeyA8 cells to measure colony formation. The colony-forming ability of the cells was reduced with increasing concentrations of fenbendazole, up to 5521 nM (Figure 2). At these high concentrations, fenbendazole caused a significant reduction in the number of colonies formed, but did not affect the proliferation rate.
We also evaluated the effect of fenbendazole on the response of EMT6 mammary tumor cells to radiation and docetaxel in vitro using dose-response curves. We found that fenbendazole did not alter the radiation dose-response curves of these cells, but did increase the antineoplastic efficacy of docetaxel when administered in combination with fenbendazole. This effect was observed in both irradiated and unirradiated tumors.
Fenbendazole is a benzimidazole drug with broad antiparasitic activity and has shown antitumor effects in several animal models. It binds to the microtubules of cancer cells and prevents their polymerization, thus resulting in cell death. Its safety margin in animals and high degree of tolerability make it a good candidate for drug repurposing as an anticancer agent.
In this study, human non-small-cell lung cancer (NSCLC) cell lines were treated with fenbendazole in vitro. Resultant cellular changes included partial alteration of the microtubule network and activation of cell-death pathways, including the mitochondrial pathway. The effect was found to be reversible when the drug was removed. The authors also performed in vivo experiments to assess the efficacy of fenbendazole against tumors in mice. Tumor volume was measured and weighed in each mouse after treatment, and results showed a significant reduction in tumor size in fenbendazole-treated mice.
The researchers used a mouse model with locally-invaded EMT6 tumors to assess the effect of fenbendazole alone or in combination with radiation. The growth curve of untreated EMT6 tumors was not altered by three 2-h treatments with fenbendazole, but the toxicity of fenbendazole to EMT6 cells was increased when treated under hypoxia, where viability decreased steeply at low drug concentrations and remained constant as doses reached the limit of solubility. The combination of fenbendazole and radiation reduced the number of tumors in mice by 50% when compared to the controls.
In addition to acting as an antiparasitic medication, fenbendazole has been shown in studies to inhibit cancer cell growth in vitro (in the laboratory) and in vivo (in animal models). In one experiment, researchers found that fenbendazole significantly reduced glucose uptake in human ovarian cancer cells. They also reported that the drug inhibited the growth of colon cancer cells in a laboratory animal model. In another experiment, researchers found that fenbendazole, along with methiazole carbamate and other related drugs, inhibited tumor progression in mice with pancreatic cancer.
In both experiments, researchers used hypoxic conditions to prevent the cells from receiving oxygen. They also observed that the cytotoxicity of fenbendazole was enhanced by hypoxia. This is probably due to the fact that hypoxic conditions decrease cellular energy and reduce the amount of tubulin available to inhibit microtubule polymerization.
However, despite these findings, it is important to remember that there are no peer-reviewed studies showing that anthelmintics can cure cancer in humans. The class of medications is currently being researched but it will likely take years to go from testing in animals to being approved for use as a cancer treatment. Until then, the best way to treat cancer is through established treatments such as chemotherapy and radiation.
Developing a new drug requires a large amount of time, money and effort. Repurposing veterinary drugs that show promising results for human use is an alternative approach to speed up this process. According to a research team from Panjab University, the broad-spectrum antiparasitic drug fenbendazole shows good promise as an anti-cancer agent. The researchers found that fenbendazole inhibited the growth of cancer cells by blocking their glucose uptake. This is a vital process in cancer cell growth, as cancer cells use up glucose for energy. The fenbendazole treatment also suppressed the growth of hepatocellular carcinoma cells by inducing apoptosis and impairing the ubiquitin-proteasome pathway.
The team compared the effects of fenbendazole to two different established anti-cancer agents. Unlike these medications, fenbendazole does not affect the viability of normal human cells. It also showed a higher degree of safety in experimental animals. The authors also tested the effect of hypoxia on fenbendazole toxicity. They sealed cultures in glass bottles with rubber gaskets, inserted needles for the influx and efflux of gases and added a humidified mixture of 95% nitrogen and 5% carbon dioxide to the culture media. They then injected the fenbendazole solution and incubated them for 2 h without breaking the hypoxia.
The Joe Tippens protocol suggests that patients should take 222 mg of fenbendazole per day, seven days a week. It is available as oral granules or as a liquid suspension and can be taken with food. The medication can be ordered through online pharmacies. fenbendazole for humans cancer