Indexed in SCIE, Scopus, PubMed & PMC
pISSN 1226-4512 eISSN 2093-3827


home Article View

Original Article

Korean J Physiol Pharmacol 2022; 26(5): 377-387

Published online September 1, 2022

Copyright © Korean J Physiol Pharmacol.

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

Deokbae Park1,#, Jung-Hee Lee2,#, and Sang-Pil Yoon3,*

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

Correspondence to:Sang-Pil Yoon

Author contributions: D.P. and S.P.Y. conceived and designed the present study; D.P. and J.H.L. performed the experiments for data acquisition and analysis; D.P. and J.H.L. interpreted the experimental results; D.P. and J.H.L. wrote the original manuscript; S.P.Y. revised the manuscript.

Received: May 25, 2022; Revised: June 7, 2022; Accepted: June 20, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


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-fluorouracil-resistant 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-fluorouracil-resistant cancer cells, and the anticancer activity of fenbendazole does not require p53 in 5-fluorouracil-resistant SNU-C5 cells.

Keywords: Apoptosis, Colorectal cancer, Drug resistance, Fenbendazole, p53