The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Anti-cancer effects of fenbendazole on 5-fluorouracil-resistant colorectal cancer cells

  • Park, Deokbae (Department of Histology, College of Medicine, Jeju National University) ;
  • Lee, Jung-Hee (Department of Cellular and Molecular Medicine, Chosun University School of Medicine) ;
  • Yoon, Sang-Pil (Department of Anatomy, College of Medicine, Jeju National University)
  • Received : 2022.05.25
  • Accepted : 2022.06.20
  • Published : 2022.09.01
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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-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

Acknowledgement

This work was supported by a research grant from the Jeju National University Hospital Research Fund of Jeju National University School of Medicine in 2020.

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