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

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.

Appraisal of Chitosan-Coated Lipid Nano-Combination with Miltefosine and Albendazole in the Treatment of Murine Trichinellosis: Experimental Study with Evaluation of Immunological and Immunohistochemical Parameters

“…Treatment with ABZ caused a significant reduction in GATA3 and a non-significant reduction in GPX1 expression, which agreed to some extent with results documented by Wu et al [ 48 ] and Kim et al [ 58 ], where ABZ showed a non-significant reduction of messenger ribonucleic acid (mRNA) expressions of GATA3 transcription factor and the mRNA expression of the antioxidant enzymes catalase, GPX1, and GPX3 used in the treatment of experimental Echinococcus multilocularis and prostate cancer, respectively. This difference might be due to different drug regimens and infections.…”

Identification of Promising Drug Candidates against Prostate Cancer through Computationally-Driven Drug Repurposing

“…Another broad-spectrum anthelminthic agent potentially repositionable against PC is Albendazole (DB00518) , which showed potent antiproliferative effects toward PC-3 and DU-145 at 0.1 µM concentration and 0.5 µM against LNCaP [ 138 ]. Unfortunately, recent studies showed that high doses of Albendazole for a prolonged time could result in toxicity according to results of the phase I trial of this compound including 2 PC patients, suggesting frequent dose monitoring [ 139 ].…”

Fucoidan/UVC Combined Treatment Exerts Preferential Antiproliferation in Oral Cancer Cells but Not Normal Cells

“…Oxidative stress promotes the antiproliferation of cancer cells [ 47 , 48 ]. Combining different oxidative stress-modulating treatments may evoke synergistic oxidative stress, leading to synergistic antiproliferation [ 49 , 50 , 51 ].…”