Research Article

Memantine activates LKB1-AMPK pathway in breast carcinoma cells

Volume: 41 Number: 4 December 29, 2020
EN

Memantine activates LKB1-AMPK pathway in breast carcinoma cells

Abstract

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. 

Keywords

References

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Details

Primary Language

English

Subjects

Structural Biology

Journal Section

Research Article

Publication Date

December 29, 2020

Submission Date

July 13, 2020

Acceptance Date

November 3, 2020

Published in Issue

Year 2020 Volume: 41 Number: 4

APA
Bali, E. B. (2020). Memantine activates LKB1-AMPK pathway in breast carcinoma cells. Cumhuriyet Science Journal, 41(4), 775-783. https://doi.org/10.17776/csj.768907

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