The cytotoxic effect of memantine and its effect on cytoskeletal proteins expression in metastatic breast cancer cell line

Abstract

<strong><em>Objective(s):</em></strong>Breast cancer is an important leading cause of death from cancer. Stathmin and tau proteins are regulators of cell motility, and their overexpression is associated with the progression and bad prognosis of breast cancer. Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is the potential inhibitor of tau protein in neurons. This study determines the effect of memantine on breast cancer cell migration and proliferation, tau and stathmin gene expression in cancer cells and its synergistic effect with paclitaxel. <br /> <strong><em>Materials and Methods: </em></strong>The cell proliferation was evaluated by MTT assay and for this purpose, MCF-7 breast cancer cells were treated with various concentration of memantine (2, 20 and 100 μg/ml). Tau and stathmin mRNA expression was evaluated through quantitative real time RT-PCR method. The migration of cancer cells treated with memantine for 24 hr was compared to non-treated cells using an <em>in vitro</em> transmembrane migration assay.<br /> <strong><em>Results:</em></strong> Incubation of breast cancer cells with memantine resulted in a dose dependent reduction in cell survival (<em>P</em>=0.0001). Paclitaxel (100 nM) showed synergistic effect with memantine (<em>P</em>=0.0001). Memantine significantly decreased tau and stathmin mRNA expression (by RT-PCR), so that 100 µmol/l of memantine decreased tau and stathmin expression by 46% (<em>P</em>=0.0341) and 33% (<em>P</em>=0.043), respectively. Migration of cells was also decreased by memantine (<em>P</em>=0.0001).<br /> <strong><em>Conclusion: </em></strong>The presented data shows that memantine reduced mRNA levels of tau and stathmin proteins and also reduced cellular migration.