Fenben (Bendazole) is a medication used to treat parasitic infections in dogs. It is not approved for use in humans, but an unlicensed veterinarian made a video claim that it cures cancer and has gone viral on Facebook and TikTok. The claims are false and the drug has not undergone human clinical trials to determine if it is safe or effective.
The benzimidazole class of drugs is known to disrupt microtubule dynamics, induce cell cycle arrest and promote apoptosis. Fenben is also a known inhibitor of P-gp, which may help explain its anthelmintic properties against parasites. In addition, benzimidazoles have been shown to inhibit glucose uptake in cancer cells due to down regulation of GLUT transporters and key glycolytic enzymes. To test whether FZ affects glucose uptake in cancer cells, a fluorescent glucose analogue 2-NBDG was added to culture supernatants of H460 and A549 cells after 1 uM FZ treatment for 4 h. Glucose uptake was reduced in both cells after FZ treatment (Fig. 8a).
Tubulin acetylation is critical for the stability of mammalian microtubules, and acetylation level has been found to correlate with cell survival in many cell types. To determine if FZ affects cellular acetylation of tubulin, NSCLC cells were treated with various microtubule targeting agents for 24 h. As expected, both nocodazole and vincristine significantly decreased acetylated tubulin, while FZ had only a modest effect. In contrast, the acetylation levels of tubulin were significantly increased following treatment with a gamma-secretase inhibitor (GSI), confirming that the observed increase in cell death after FZ treatment is independent of GSI.
FZ has been reported to be a weak P-gp inhibitor31,32. We therefore compared the growth inhibition of cancer cells by FZ in the presence and absence of the P-gp inhibitor verapamil. The results indicate that the inhibitory effect of FZ is largely independent of P-gp and is mainly caused by its disruption of microtubule dynamics.
The growth and radiation response of EMT6 tumors in BALB/cRw mice were examined after three daily i.p. injections of Fenbendazole or vehicle. Tumors were allowed to grow to a volume of 1000 mm3 and then randomly assigned to groups that either received Fenbendazole, or no drug or received local tumor irradiation in combination with the drug. Mice were euthanized when tumors reached this volume, and the number of lung metastases was compared between mice that did or did not receive irradiation in conjunction with fenbendazole treatment.
No irradiated tumors grew in Fenbendazole plus x-ray treated mice, suggesting that FZ and irradiation had a synergistic effect on eliminating the preexisting tumor. This result was confirmed in a subsequent experiment, where the same protocol was repeated but with an additional treatment of the P-gp inhibitor verapamil. fenben