Korean J Physiol Pharmacol.  2022 Sep;26(5):377-387. 10.4196/kjpp.2022.26.5.377.

Anti-cancer effects of fenbendazole on 5-fluorouracil-resistant colorectal cancer cells

  • 1Department of Histology, College of Medicine, Jeju National University, Jeju 63243, Korea
  • 2Department of Cellular and Molecular Medicine, Chosun University School of Medicine, Gwangju 61452, Korea
  • 3Department of Anatomy, College of Medicine, Jeju National University, Jeju 63243, Korea


Benzimidazole anthelmintic agents have been recently repurposed to overcome cancers resistant to conventional therapies. To evaluate the anti-cancer effects of benzimidazole on resistant cells, various cell death pathways were investigated in 5-fluorouracil-resistant colorectal cancer cells. The viability of wild-type and 5-fluorouracil-resistant SNU-C5 colorectal cancer cells was assayed, followed by Western blotting. Flow cytometry assays for cell death and cell cycle was also performed to analyze the anti-cancer effects of benzimidazole. When compared with albendazole, fenbendazole showed higher susceptibility to 5-fluorouracil-resistant SNU-C5 cells and was used in subsequent experiments. Flow cytometry revealed that fenbendazole significantly induces apoptosis as well as cell cycle arrest at G2/ M phase on both cells. When compared with wild-type SNU-C5 cells, 5-fluorouracilresistant SNU-C5 cells showed reduced autophagy, increased ferroptosis and ferroptosis-augmented apoptosis, and less activation of caspase-8 and p53. These results suggest that fenbendazole may be a potential alternative treatment in 5-fluorouracilresistant cancer cells, and the anticancer activity of fenbendazole does not require p53 in 5-fluorouracil-resistant SNU-C5 cells.


Apoptosis; Colorectal cancer; Drug resistance; Fenbendazole; Fenbendazole
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