Anti-Cancer Effects of Fenben (Mebendazole)

The anthelmintic drug fenben (Mebendazole) has recently been repurposed as a cancer treatment. The benzimidazole exhibits antitumor activity in cell culture models and in vivo in animals. It is able to overcome resistance to conventional chemotherapy in a 5-fluorouracil-resistant colorectal cancer cell line. It also has a direct effect on the tumor microtubules, blocking mitosis, and suppresses RAS-related signaling pathways in cells with KRAS mutation.

We studied the anti-cancer effects of fenbendazole in wild-type and 5-fluorouracil-resistant SNU-C5 and SNU-C5/5-FUR CRC cells using cell viability assays, Western blotting, and flow cytometry. Severe hypoxia dramatically increased the toxicity of 2-h treatments with fenbendazole in both cells, but the IC50 values were still close to those of the drug at DMSO concentrations. In both cell types, fenbendazole induces autophagy by Beclin-1 and inhibits LC3-I and Atg16L1 expression to promote apoptosis through the p53 pathway. It also triggers apoptosis via necroptosis through decreased expression of GPX4 and Beclin-1 in SNU-C5/5-FUR cells.

Time-dependent fenbendazole antiproliferative effects were also evaluated in both cells. The drug rapidly decreased the proliferation of both cells and exhibited stronger inhibitory effects in SNU-C5/5-FUR than in wild-type cells.

The anti-tumor effects of fenbendazole were further confirmed in an in vivo model in BALB/c mice bearing human lung adenocarcinoma (AM4) cells. When 1 mg/mouse of fenbendazole was orally administered to these mice every 2 days for 12 days, tumors showed considerable shrinkage. No local invasion or lymph node metastases were observed.