Reducing the Effective Dosage of Flutamide on Prostate Cancer Cell Lines Through Combination With Selenium Nanoparticles: An In-Vitro Study Publisher Pubmed



Oskouie IM¹ ; Khatami F¹ ; Dezfuli AS² ; Mashhadi R¹ ; Mirzaei A¹ ; Hashemi Dougaheh SN¹ ; Ghajar HA¹ ; Heshmat R³ ; Kazem Aghamir SM¹ Show Affiliations
Source: PLoS ONE Published:2025

Abstract

Objective Objective of the study was to evaluate the therapeutic potential of selenium nanoparticles (SeNPs) in combination with flutamide for treating prostate cancer (PCa) cell lines. The goal was to reduce the dosage of flutamide to decrease its side effects, especially hepatotoxicity. Materials and methods PC3, LnCAP, and DU145 cell lines were treated with varying concentrations of SeNPs and Flutamide to determine IC50 values using the MTT assay. Subsequently, the IC50 concentration of flutamide was reduced by 50% and different concentrations of SeNPs were added to determine new IC50 concentrations of the combinations. Annexin-V/ PI staining was performed to assess the apoptosis rate. The DNA cell cycle was analyzed using the PI staining technique. Migration, proliferative capability, and nucleus morphology of the cells were evaluated through the scratch-wound assay, colony-forming assay, and Hoechst staining, respectively. The expression of SNAIL, KLK3, E-cadherin, VEGF-C, HIF-1α, Bcl2, and BAX were examined using real-time PCR. Results All treated groups significantly increased early and late apoptosis rate of the PCa cell lines, and induced SubG1/G1 arrest in the cell cycle assay, compared to the control group. Significant inhibition of migration potential and colony formation was observed in all treated groups. Our results suggest that the combination group (50% decrease of Flutamide dosage) treatment upregulated apoptosis-related genes and KLK3, and downregulated genes involved in angiogenesis and proliferation similar to Flutamide alone (p > 0.05). Conclusion It is suggested that simultaneous administration of SeNPs and flutamide could potentially reduce the effective dosage of flutamide and decrease its adverse effects. © 2025 Menbari Oskouie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.