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

Affiliations
  • 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

Abstract

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.

Keyword

Apoptosis; Colorectal cancer; Drug resistance; Fenbendazole; Fenbendazole
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