A drug commonly used to treat parasitic worms may kill cancer cells and prevent them from growing in the future, according to new research. The findings, published in Scientific Reports, come from a study on fenbendazole (also known as mebendazole), which was originally developed to fight roundworm, hookworm and other parasitic infections by cutting off their supply of nutrients. It does this by interfering with the formation of a protein called tubulin. Tubulin is both the skeleton of the cell and a highway for transporting food to cells. When mebendazole inhibits tubulin’s formation, it starves the parasite to death. The same mechanism could also work in cancer cells, according to the researchers at Johns Hopkins University.
The team’s previous work showed that mebendazole interferes with a complex set of processes, including mitosis, which is the process by which a cell divides. It does this by weakening the forces that pull chromosomes apart during this stage of cell division. As a result, chromosomes are evenly distributed between the two daughter cells. The researchers’ latest study showed that fenbendazole, a chemical analog of mebendazole, has similar effects in pancreatic cancer cells. “Fenbendazole blocks a key step of cell division, the formation of the mitotic spindle,” says senior author Michael Riggins, Ph.D., a professor in the department of Cell Biology and Molecular Genetics at Johns Hopkins Medicine. “We believe this is why it’s effective in pancreatic cancer and could potentially be useful in other cancers as well.”
In this current study, the scientists tested fenbendazole on human colorectal cancer cells. They found that the drug partially alters the microtubule network around the nucleus, a change that triggers cancer cell death. The researchers also observed increased expression of autophagy proteins, including Beclin-1 and LC3-I, in the cells treated with fenbendazole.
To test the effect of fenbendazole on human lymphoma xenografts in mice, they fed the animals either a normal diet or one supplemented with vitamins and fenbendazole. They found that the fenbendazole diet significantly inhibited tumor growth compared with the vitamin-only diet.
The fenbendazole treatment also led to a reduction in tumor-associated inflammation and apoptosis in the mice. To further examine the underlying mechanisms, the researchers used a combination of techniques, including Western blotting to detect autophagy and necroptosis-related proteins in the cells. They also measured the levels of phosphorylated RIP, pMLKL and pCASP8 in the cells. These are all markers of necroptosis, which is a form of programmed cell death. The results show that fenbendazole reduces the growth of colorectal cancer cells in mice, and in part by triggering apoptosis and inducing autophagy. (The authors acknowledge funding from the Virginia and D.K. Ludwig Fund for Cancer Research.) This does not mean that fenbendazole will cure cancer in humans or prevent it from recurring, but it’s an interesting finding worth exploring in future studies. It is important to note that there are several established treatments for cancer, including surgery, chemotherapy and radiation therapy, which can all help patients with their disease. fenbendazole for cancer