Albendazole exerts antiproliferative effects on prostate cancer cells by inducing reactive oxygen species generation

Kim,Ukjin; Shin,Changsoo; Kim,C-Yoon; Ryu,Bokyeong; Kim,Jin; Bang,Junpil; Park,Jae-Hak

doi:10.3892/ol.2021.12656

Albendazole exerts antiproliferative effects on prostate cancer cells by inducing reactive oxygen species generation

Authors:
- Ukjin Kim
- Changsoo Shin
- C-Yoon Kim
- Bokyeong Ryu
- Jin Kim
- Junpil Bang
- Jae-Hak Park
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Affiliations: Department of Laboratory Animal Medicine, Research Institute for Veterinary Science, BK21 PLUS Program for Creative Veterinary Science Research, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea, Department of Energy Resources Engineering, Seoul National University, Seoul 08826, Republic of Korea, Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul 05029, Republic of Korea
Published online on: March 18, 2021 https://doi.org/10.3892/ol.2021.12656
Article Number: 395

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Abstract

Benzimidazole derivatives are used for their antihelmintic properties, but have also been reported to exert anticancer effects. In the present study, the anticancer effects of albendazole on prostate cancer cells were assessed using proliferation, clonogenic and migration assays. To investigate the anticancer mechanisms of albendazole, reactive oxygen species (ROS) levels were measured, and the expression of genes associated with oxidative stress and Wnt/β‑catenin signaling was confirmed by reverse transcription‑quantitative PCR and western blotting. Albendazole selectively inhibited the proliferation of the PC3, DU145, LNCaP and AT2 prostate cancer cell lines at concentrations that did not affect the proliferation of a normal prostate cell line (RWPE‑1). Albendazole also inhibited the colony formation and migration of PC3 and DU145 cells, as well as inducing ROS production. Diphenyleneiodonium chloride, an inhibitor of NADPH oxidase (NOX), one of the sources of ROS, decreased basal ROS levels in the PC3 and DU145 cells, but did not reduce albendazole‑associated ROS production, suggesting that ROS production following albendazole treatment was NOX‑independent. The anticancer effect was decreased when albendazole‑induced ROS was reduced by treatment with antioxidants (glutathione and N‑acetylcysteine). Furthermore, albendazole decreased the mRNA expression of CDGSH iron sulfur domain 2, which regulates antioxidant activity against ROS, as well as the antioxidant enzymes catalase, and glutathione peroxidase 1 and 3. Albendazole also decreased the mRNA expression of catenin β1 and transcription factor 4, which regulate Wnt/β‑catenin signaling and its associated targets, Twist family BHLH transcription factor 1 and BCL2. The albendazole‑related decrease in the expression levels of oxidative stress‑related genes and Wnt/β‑catenin signaling proteins was thought to be associated with ROS production. These results suggest that the antihelmintic drug, albendazole, has inhibitory effects against prostate cancer cells in vitro. Therefore, albendazole may potentially be used as a novel anticancer agent for prostate cancer.

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