Anti-cancer effects of fenbendazole on 5-fluorouracil-resistant colorectal cancer cells |
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Authors: | Deokbae Park Jung-Hee Lee Sang-Pil Yoon |
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Affiliation: | 1.Department of Histology, College of Medicine, Jeju National University, Jeju 63243, Korea;2.Department of Cellular and Molecular Medicine, Chosun University School of Medicine, Gwangju 61452, Korea;3.Department of Anatomy, College of Medicine, Jeju National University, Jeju 63243, Korea |
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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. |
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Keywords: | Apoptosis Colorectal cancer Drug resistance Fenbendazole p53 |
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