Mebendazole Suppresses Tumor Growth and Hinders the Invasion of Triple-Negative Breast Cancer in Model Systems by Disrupting RAN-GTP Regulation

Abstract

Due to the lack of targeted therapies, triple-negative breast cancer (TNBC), one of the most aggressive types of cancer, has a poor prognosis and a high death rate. TNBC frequently metastasizes to the brain, bones, and lungs. Studies have demonstrated a correlation between the metastatic behavior of A594 lung cancer cells and MDA-MB-231 breast cancer cells and the overexpression of the RAN GTP (RAN) gene. Using a variety of biological assays, this study sought to investigate mebendazole’s potential as an anticancer agent by specifically targeting the RAN gene. Both MDA-MB-231 breast cancer cells (IC50 7.5 μM) and A549 lung cancer cells (IC50 48.5 μM) were shown to be resistant to mebendazole’s ability to promote cell growth. The cytotoxic effect of mebendazole via the apoptotic pathway was confirmed by Annexin V assays on both cell lines. Furthermore, mebendazole demonstrated enhanced efficacy against TNBC by halting the cell cycle, preventing colony formation, invasion, and migration, and reducing RAN GTPase expression in both cell lines.