Anti-cancer effects of fenbendazole on 5-fluorouracil-resistant colorectal cancer cells
10.4196/kjpp.2022.26.5.377
- Author:
Deokbae PARK
1
;
Jung-Hee LEE
;
Sang-Pil YOON
Author Information
1. Department of Histology, College of Medicine, Jeju National University, Jeju 63243, Korea
- Publication Type:Original Article
- From:The Korean Journal of Physiology and Pharmacology
2022;26(5):377-387
- CountryRepublic of Korea
- Language:English
-
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.
