Fenbendazole was originally designed to cure parasites by selectively blocking the synthesis of microtubules by binding to β-tubulin. This stops the polymerization of tubulin dimers in cells of parasites and causes parasite death.
Surprisingly, it seems that fenbendazole as well as other benzimidazoles exhibit a similar effect against tumor cells. Today it is thought that there are 3 main mechanisms in which fenbendazole kills cancer:
1) Apoptosis induction. The anti-tumor effect is believed to be through the interaction of the drug with the β-tubulin leading to cell cycle arrest and cytotoxic.
2) Inhibition of glucose uptake in cancer cells. Malignant cells are known to have an enormous glucose uptake. Cancer cells normally consume glucose 200 times faster than ordinary cells due to aerobic glycolysis (Warburg effect). This can be seen in PET scans – the metabolically active sites, which use more radioactive glucose can be clearly seen and are generally thought to be cancerous tumors or sites of inflammation.
Fenbendazole limits cancer cell fueling with sugar by limiting the glucose uptake, decreasing the amount of GLUT transporters (canals that take glucose into the cancer cells from the blood) and the enzyme hexokinase 2. The latter is important for cancer cell survival, it helps the tumors thrive by generating more sugar and accelerating lactic acidosis in the extracellular matrix. (Ref.1, Ref.2)
3) Reactivation of the p53 gene. This work mechanism is still relatively controversial, and more studies need to be done to confirm that fenben causes this action. (Ref.)
However, there is an increasing number of studies that confirm the fact that fenbendazole might truly increase the strongest tumor suppressor in our bodies – p53. (Ref.)
It is known that elephants have 20 copies of the p53 gene in their genome and humans have only 1 copy. Interestingly, that is why elephants get cancer less frequently than us, humans. Despite these creatures having a huge body size, a larger number of cells and a bigger number of potential genetic mutations.