Fenben (FZ) is a synthetic, non-steroidal, anti-parasitic agent with demonstrated radiosensitizing effects in cancer cells. It also exhibits anthelmintic activity in animals. FZ has recently been promoted on social media platforms including TikTok by unlicensed veterinarians as a dog deworming medicine that cures human cancer. These claims are highly misleading and should be of great concern to the public. In fact, the unlicensed veterinarian has been reprimanded by the College of Veterinarians in British Columbia for making these claims in his videos on TikTok.
Molecular characterization of fenben has shown that it inhibits microtubule formation and induces cell death by multiple mechanisms. These mechanisms include disruption of microtubule dynamics, p53 activation and modulation of genes involved in several cellular pathways. FZ also inhibits glucose uptake in cancer cells through down regulation of GLUT transporters and key glycolytic enzymes. It displays effective radiation sensitization in xenografts and prevents the growth of irradiated tumors in mice.
To evaluate the effects of FZ on radiation response, EMT6 cancer cells were irradiated at graded doses under either aerobic or hypoxic conditions and assayed for cell survival using a colony formation assay. The data are reported as both surviving fractions and yield-corrected surviving fractions (YCSF), which take into account the number of cells that die in each treatment group at the end of the experiment. Cells were treated with fenbendazole or vehicle for 2 or 24 h and then exposed to radiation. Radiation sensitive cultures were able to grow to almost four times their initial volume without being killed by fenbendazole, and the effects of FZ on radiation sensitization in cells grown under severe hypoxia are illustrated in Figure 1.
To determine the molecular mechanism by which fenben induced radiation sensitization, A549 cancer cells were synchronized with serum starvation and treated with different concentrations of fenbendazole for different periods of time. Cells were lysed and fractionated into soluble (S), cytosolic (C) and mitochondrial (M) extracts for immunofluorescence and western blot analysis. Treatment of cells with fenbendazole caused a rapid decrease in the cytosolic and mitochondrial tubulin network. This was associated with a delay in progression through the mitotic checkpoint and a subsequent increase in cyclin B1 levels accompanied by a reduction in anaphase-promoting complex (APC) activity. This led to mitotic catastrophe and apoptosis. Thus, fenbendazole alters the microtubule network in cancer cells and promotes apoptosis via multiple mechanisms, thereby rendering them radiosensitized. The pleiotropic effects of this agent suggest that it may be a candidate for anti-neoplastic therapy. fenben