Memantine shifts cancer cell metabolism via AMPK1/2 mediated energetic switch in A549 lung cancer cells

Authors

DOI:

https://doi.org/10.17179/excli2020-2890

Keywords:

Memantine, lung cancer, drug re-purposing, cancer cell metabolism

Abstract

Memantine is used to prevent glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer’s disease. As glutamine is one of the major source of anabolism in fast growing cancer cells, we aimed to interfere with the cancer cell metabolism in A549 lung cancer cells by using memantine. The effects of memantine on cell cycle progression and cell death in A549 cells were assessed by MTT assay and PI staining. Cells were treated with 0.25 mM memantine for 48 hours and then cell metabolism (AMPKA1, AMPKA2, HIF1A, B-catenin, PKM), apoptosis (p53, p21, Bax, Bcl-XL, NOXA, PUMA) and autophagy related (LC3B-I, LC3B-II, SQSTM1) mRNA and protein expressions were investigated by RT-qPCR and western blotting. Memantine decreased cell viability significantly in a concentration-dependent manner by inducing G0/G1 cell cycle arrest. Our results suggest that memantine activates AMPK1/2 significantly (p=0.039 and p=0.0105) that led cells through apoptosis and autophagy by decreasing cancer cell metabolism regulators like HIF1A, B-catenin and PKM as the consequence of this energetic shift. Memantine represents a useful tool to target metabolism in cancer cells. Therefore, it might be used a new repurposed drug in cancer treatment.

Author Biography

Funda Demirtas Korkmaz, Department of Medical Biology, Faculty of Medicine, Giresun University, Giresun, Turkey

https://orcid.org/0000-0003-3978-9427

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Published

2021-02-04

How to Cite

Albayrak, G., & Demirtas Korkmaz, F. . (2021). Memantine shifts cancer cell metabolism via AMPK1/2 mediated energetic switch in A549 lung cancer cells. EXCLI Journal, 20, 223–231. https://doi.org/10.17179/excli2020-2890

Issue

Vol. 20 (2021)

Section

Original articles

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Copyright (c) 2021 Gulsah Albayrak, Funda Demirtas Korkmaz

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