Reducing the effective dosage of flutamide on prostate cancer cell lines through combination with selenium nanoparticles: An in-vitro study

TL;DR

This study shows that combining selenium nanoparticles with flutamide can reduce the needed dose of flutamide in prostate cancer cells, potentially lowering side effects.

Contribution

The novel finding is that selenium nanoparticles can effectively reduce flutamide dosage while maintaining therapeutic effects in prostate cancer cells.

Findings

Combining SeNPs with flutamide increased apoptosis and induced cell cycle arrest in prostate cancer cell lines.

The combination significantly inhibited migration and colony formation of cancer cells.

Gene expression changes were similar to flutamide alone, suggesting equivalent efficacy at lower doses.

Abstract

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.

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.

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).

It is suggested that simultaneous administration of SeNPs and flutamide could potentially reduce the effective dosage of flutamide and decrease its adverse effects.

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