MCF7 cell line
cancer metabolism
glutamine synthetase
glycolysis
luminal breast cancer
Journal
EXCLI journal
ISSN: 1611-2156
Titre abrégé: EXCLI J
Pays: Germany
ID NLM: 101299402
Informations de publication
Date de publication:
2023
2023
Historique:
received:
27
06
2023
accepted:
07
08
2023
medline:
2
10
2023
pubmed:
2
10
2023
entrez:
2
10
2023
Statut:
epublish
Résumé
The glutamine synthetase path is one of the most important metabolic pathways in luminal breast cancer cells, which plays a critical role in supplying glutamine as an intermediate in the biosynthesis of amino acids and nucleotides. On the other hand, glycolysis and its dominant substrate, glucose, are the most critical players in cancer metabolism. Accordingly, targeting these two critical paths might be more efficient in luminal-type breast cancer treatment. MCF7 cells were cultivated in media containing 4.5, 2, and 1 g/L glucose to study its effects on GLUL (Glutamate Ammonia Ligase) expression. Followingly, high and low glucose cell cultures were transfected with 220 pM of siGLUL and incubated for 48 h at 37 ºC. The cell cycle progression and apoptosis were monitored and assessed by flow cytometry. Expression of GLUL, known as glutamine synthetase, was evaluated in mRNA and protein levels by qRT-PCR and western blotting, respectively. To examine the migration and invasion capacity of studied cells exploited from wound healing assay and subsequent expression studies of glutathione-S-transferase Mu3 (GSTM3) and alfa-enolase (ENO1). Expression of GLUL significantly decreased in cells cultured at lower glucose levels compared to those at higher glucose levels. siRNA-mediated knockdown of GLUL expression in low glucose cultures significantly reduced growth, proliferation, migration, and invasion of the MCF7 cells and enhanced their apoptosis compared to the controls. Based on the results, GLUL suppression down-regulated GSTM3, a main detoxifying enzyme, and up-regulated Bax. According to the role of glycolysis as a ROS suppressor, decreased amounts of glucose could be associated with increased ROS; it can be considered an efficient involved mechanism in this study. Also, increased expression of Bax could be attributable to mTOR/AKT inhibition following GLUL repression. In conclusion, utilizing GLUL and glycolysis inhibitors might be a more effective strategy in luminal-type breast cancer therapy. See also Figure 1(Fig. 1).
Identifiants
pubmed: 37780942
doi: 10.17179/excli2023-6287
pii: 2023-6287
pmc: PMC10539544
doi:
Types de publication
Journal Article
Langues
eng
Pagination
847-861Informations de copyright
Copyright © 2023 Karimpur Zahmatkesh et al.
Déclaration de conflit d'intérêts
The authors declare no potential conflicts of interest.
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