Effects of Mebendazole and Flutamide Combination in Prostate Cancer Cell Lines: a Comprehensive in Vitro Analysis

Abstract

Background/Aims: The aim of this research was to use Mebendazole as an anticancer candidate to reduce the dose of Flutamide and reduce its side effects. Method: In this in vitro study, we evaluated the effect of Mebendazole, Flutamide and Mebendazole-Flutamide combination therapy in LNCaP, DU145 and PC3 cell lines as representatives of human prostate cancer. The assessment includes scratch-wound assay, colony formation assay, flow cytometric analysis of apoptosis and DNA cell cycle, real-time PCR (BAX/BCL2, E-cadherin, N-cadherin, Snail, HIF1 alpha, VEGFC, KLK3, TUBB1 and TUBB3 genes). Results: To determine IC50 levels, cell lines were exposed to different concentration of the drugs. Our data indicated that IC50 values for Mebendazole (55 mu M) and for 3 cell lines and flutamide (12 mu M and 10 mu M) for PC3 and LNCaP/DU145 respectively, with MTT were approved by flow cytometry in a dose and time-dependent manner which was as a consequence of cell cycle arrest at G1/S phase. Furthermore, for the first time, we offered that combination of mebendazole and flutamide produced a greater inhibitory effect on cell viability, colony formation, and migration than either agent alone at the tested concentrations. The combination treatment also increased apoptotic cell populations and upregulated the BAX/BCL2 mRNA ratio and E-cadherin expression in all three cell lines (P<0.01) and downregulated the expression of TUBB1 in DU145 and TUBB3 genes in DU145 and PC3 cell lines (P<0.01). Conclusion: Mebendazole in combination with flutamide reduced dose of flutamide and increased the sensitivity of prostate cancer cells to treatment. Therefore, this combination may represent a promising in vitro strategy that warrants further mechanistic and in vivo investigation.