Memantine activates LKB1-AMPK pathway in breast carcinoma cells

Drug repositioning that is a screening of presently approved drugs for already unknown indications is therapeutically necessary and influential for drug discovery. In this study, it was aimed to research whether memantine as a repositioned drug can activate the LKB1-AMPK pathway in breast carcinoma cells by triggering tumor suppressor genes LKB1, AMPK, its downstream targets 40S ribosomal S6 kinases (S6K1 and S6K2), and eukaryotic initiation factor 4E-binding protein 4E-BP1. It was also evaluated its apoptotic effect by detecting the gene expressions of Caspase 7 and NOXA. Thus, MCF-7 cells were treated with 250 µM memantine for 48 h, and its cytotoxic effect was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. AMPKα1, AMPKα2, S6K1, S6K2, 4E-BP1, Caspase 7 and NOXA gene expression levels were measured by quantitative real-time polymerase chain reaction. The results clearly revealed that memantine inhibited MCF-7 cell proliferation and activated the LKB1-AMPK pathway by reducing S6K1, S6K2, and 4EBP1 gene expressions. Memantine also augmented the gene expressions of Caspase 7 and NOXA. The findings reveal a molecular mechanism for the first time that may contribute to the anti-cancer effect of memantine to prevent or treat breast cancer. But further research should be performed to better understand its anti-cancer action.