Fenben is a common medication used to treat rodent pinworms (roundworms, hookworms, whipworms, and some tapeworms) (common brand names include Pancur and Safe-Guard). Recently, it has become known as an effective cancer treatment. In combination with vitamins, fenben interferes with sugar uptake by cancer cells and therefore limits the tumor’s growth.
Research has shown that cancer cells consume a lot of glucose, which is its primary fuel source. Benzimidazole drugs such as fenben have been found to be very effective against various types of cancer and other parasites in animal models. Moreover, these compounds have a similar structure as cellular microtubules and therefore act as cytotoxic anticancer agents by disrupting the formation of microtubules.
The anthelminthic drug, fenbendazole (FZ) inhibits the activity of two enzymes in the mitochondrial tricarboxylic acid cycle (TCA): fumarate reductase and succinate dehydrogenase. Succinate is a TCA cycle metabolite that accumulates in malignant cell lines due to down regulation of SDH gene expression and promotes tumor progression.
To investigate the antitumor effect of fenbendazole, we treated hexokinase II (HKII)-overexpressing human NSCLC H460 cells with varying concentrations of fenbendazole for 24 h. We showed that FZ significantly altered glucose uptake by cancer cells and impaired the enzymatic activity of HKII, which resulted in decreased glycolysis. This reduced glycolysis is thought to be a major reason for the observed decrease in tumor size of the fenbendazole treated group in the mouse model. In addition, fenbendazole increased the expression of p53 and downregulated several genes related to TCA cycle and cellular energy metabolism. fenben cancer treatment