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http://dx.doi.org/10.14405/kjvr.2020.60.2.79

Involvement of reactive oxygen species in the anti-cancer activity of fenbendazole, a benzimidazole anthelmintic  

Han, Yong (Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, Jeju National University)
Joo, Hong-Gu (Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, Jeju National University)
Publication Information
Korean Journal of Veterinary Research / v.60, no.2, 2020 , pp. 79-83 More about this Journal
Abstract
Fenbendazole (FBZ) is a benzimidazole anthelmintic that has been widely used in treatments for gastrointestinal parasites including pinworms and roundworms in animals. Recently, some studies demonstrated that FBZ has anti-cancer effects related to disruption of microtubule polymerization. In this study, we investigated whether FBZ has anti-cancer activity in HL-60 cells, a human leukemia cell line, and assessed its relationship with the production of reactive oxygen species (ROS). FBZ treatment at 0.25-1 μM significantly decreased the metabolic activity of HL-60 cells. The mitochondrial membrane potential of FBZ-treated HL-60 cells decreased in a concentration-dependent manner. Apoptosis analysis using annexin V-FITC/propidium iodide staining demonstrated that 1 μM FBZ increased the percentages of cells in apoptosis and necrosis. In addition, Hoechst 33342 staining showed the presence of broken nuclei in HL-60 cells treated with 0.5 and 1 μM FBZ. To investigate the anti-cancer mechanism of FBZ, HL-60 cells were treated with FBZ in the absence or presence of N-acetyl cysteine (NAC), an inhibitor of ROS production. NAC significantly recovered the decreased metabolic activity of HL-60 induced by 0.5 and 1 μM FBZ treatments. This study provides evidence that FBZ has anti-cancer activity in HL-60 cells provided, in part, via ROS production.
Keywords
fenbendazole; anti-cancer activity; HL-60 cells; reactive oxygen species; N-acetyl cysteine;
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