Fenben cancer treatment works by disrupting normal cellular processes that both viruses and some cancer cells use to grow and spread. A team led by Stanford scientists has discovered that a broad-spectrum anthelminthic drug used in horses called fenbendazole (methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl) carbamate, also known as mebendazole) and already approved for human use to treat parasitic worm infections can shrink tumors in mice and potentially stop them from spreading. The results of the study appear in the Jan. 22 issue of Science Translational Medicine.
The researchers tested the antitumor activity of fenbendazole in cultured human cancer cell lines and found that it reduced their growth by both cytotoxic and cytostatic mechanisms. The drug interfered with the cell cycle, and caused apoptosis in both 5-FU-sensitive and resistant colorectal cancer cells.
It also interfered with glucose uptake, a common feature of cancer cells that requires large amounts of sugar for energy. This led to a dramatic decrease in cell numbers with increasing concentrations of the drug. The researchers also tested fenbendazole’s effects in vivo by giving it to mice with xenografted A549 colon cancer tumours. After 12 days of oral administration, fenbendazole reduced tumor size and weight and lowered hemoglobin levels in the tumors, which is a marker for decreased tumor vascularity.
The team also found that fenbendazole’s effect in vitro was not related to its affinity for microtubules, but rather the ability of the drug to inhibit glycolysis by suppressing expression of genes involved in glycolysis. Specifically, fenbendazole reduced the expression of hexokinase II and glut-4 transporter, both known to promote glycolysis and suppress mitochondria-induced apoptosis in cells. These results suggest that fenbendazole may act as a synergistic agent in combination with chemotherapy and radiation treatments.
This work supports previous studies that showed combining antihelmintics with other drugs, such as the hypoxia-selective nitroheterocyclic cytotoxins and radiosensitizers vinblastine and temozolomide, can potentiate their therapeutic effects in glioblastoma cancer cells. The research was funded by the National Institutes of Health and the Stanford Cancer Center.