Benzimidazole Cures Cancer
Benzimidazole anthelmintic drugs are used for the control of parasites in livestock and cats. These drugs have been repurposed to treat and prevent resistance to conventional chemotherapy agents such as 5-fluorouracil (FFU). The authors found that fenbendazole induces both p53-dependent and -independent cell death in wild-type and FFU-resistant CRC cells, and cell cycle arrest at G2/M phase via p53-p21 pathways in resistant cells. The toxicity of fenbendazole was enhanced by hypoxia. IC50 values were approximately 10-fold higher in hypoxia, and fenbendazole induced a steep decrease in cell viability that plateaued at micromolar concentrations of the drug. The fenbendazole-induced decrease in viability was associated with apoptosis, but not with autophagy or ferroptosis. In contrast, p53-independent apoptosis and ferroptosis augmented by decreased expression of GPX4 were observed in SNU-C5/5-FUR cells.
In addition to promoting apoptosis and cell cycle arrest, fenbendazole increased glucose uptake by H460 and A549 cancer cells, presumably to meet the energy needs of rapidly growing cancer cells. The authors also found that fenbendazole induced mitochondrial damage in colorectal cancer cells, leading to the generation of reactive oxygen species that trigger caspase-3-poly (ADP-ribose) polymerase (PARP)-dependent pathways.
To evaluate the effects of fenbendazole in x-ray radiation-irradiated tumors, mice bearing EMT6 cancer cells were treated with three daily i.p. injections of fenbendazole alone or with 10 Gy irradiation. The growth curve of the unirradiated tumors did not change after treatment with fenbendazole, but fenbendazole in combination with x-rays significantly inhibited the growth of the irradiated tumors.fenbendazole cures cancer