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

The aim of this research was to use Mebendazole as an anticancer candidate to reduce the dose of Flutamide and reduce its side effects.

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, HIF1α, VEGFC, KLK3, TUBB1 and TUBB3 genes).

To determine IC50 levels, cell lines were exposed to different concentration of the drugs. Our data indicated that IC50 values for Mebendazole (55μM) and for 3 cell lines and flutamide (12μM and 10μM) 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).

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.