Analysis of Growth-inhibitory Mechanism of Flubendazole in Malignant Melanoma Cells

Analysis of growth-inhibitory mechanisms of flubendazole in malignant melanoma cells Malignant skin melanoma is at its advanced stage highly aggressive and chemoresistant to almost all currently available therapies. Moderns efforts are thus aimed to identify new targets in melanoma cells or to take advantage of novel indications of already approved drugs - a process called drug repurposing. This work was focused on evaluation of cell growth inhibitory properties of one such drug - flubendazole (FLU) - a widely used anthelmintic compound belonging to benzimidazole family. This drug specifically interacts with β-tubulin, which results in disruption of microtubule structure and function in the exposed cells. Several members of the benzimidazole family (including FLU) have already shown the growth inhibitory potential in tumor cells derived from breast, colon, blood and nervous system malignancies. Still, the specific activity of FLU in malignant melanoma has not been tested to the date. Cytotoxicity of FLU was tested in three malignant melanoma cell lines representing diverse melanoma molecular types (A-375, BOWES and RPMI-7951) during up to 72 hours using WST-1 and x-CELLigence assays. Based on achieved IC50 from individual cell lines, the 1 µM FLU concentration was selected for further testing. While..