Breast Cancer Research and Treatment

, Volume 171, Issue 3, pp 581–591 | Cite as

Protein N-glycosylation alteration and glycolysis inhibition both contribute to the antiproliferative action of 2-deoxyglucose in breast cancer cells

  • Audrey Berthe
  • Marie Zaffino
  • Claire Muller
  • François Foulquier
  • Marine Houdou
  • Céline Schulz
  • Frédéric Bost
  • Elia De Fay
  • Sabine MazerbourgEmail author
  • Stéphane Flament
Preclinical study



Cancer cells often elicit a higher glycolytic rate than normal cells, supporting the development of glycolysis inhibitors as therapeutic agents. 2-Deoxyglucose (2-DG) is used in this context due to its ability to compete with glucose. However, many studies do not take into account that 2-DG inhibits not only glycolysis but also N-glycosylation. Since there are limited publications on 2-DG mechanism of action in breast cancer, we studied its effects in breast cancer cell lines to determine the part played by glycolysis inhibition and N-linked glycosylation interference.

Methods and Results

2-Deoxyglucose behaved as an anticancer agent with a similar efficiency on cell number decrease between the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 breast cancer cells. It also interfered with the N-linked glycosylation process in both cell lines as illustrated by the migration profile of the lysosomal-associated membrane protein 2 and calumenin. These results are reinforced by the appearance of an abnormal Man7GlcNAc2 structure both on lipid-linked oligosaccharides and N-linked glycoproteins of 2-DG incubated MDA-MB-231 cells. Besides, 2-DG-induced a transient endoplasmic reticulum stress that was more sustained in MDA-MB-231 cells. Both changes were abrogated by mannose. 2-DG, even in the presence of mannose, decreased glycolysis in both cell lines. Mannose partially reversed the effects of 2-DG on cell numbers with N-linked glycosylation interference accounting for 37 and 47% of 2-DG anti-cancerous effects in MDA-MB-231 and MCF-7 cells, respectively.


N-linked glycosylation interference and glycolysis disruption both contribute to the anticancer properties of 2-DG in breast cancer cells.


Breast cancer 2-Deoxyglucose Glycolysis N-Glycosylation Endoplasmic reticulum stress 





Binding immunoglobulin protein


Transcription factor CEBP homologous protein


Endoplasmic reticulum






Half maximal inhibitory concentration


Inositol requiring enzyme 1


Lysosomal-associated membrane protein 2


Lipid-linked oligosaccharides




N-linked glycoproteins


Pancreatic endoplasmic reticulum kinase-like endoplasmic reticulum kinase


Unfolded protein response


X-box-binding protein-1



This project was funded by University of Lorraine and Région of Lorraine. Audrey Berthe and Claire Muller were recipient of a PhD grant of the “Ministère de l’Enseignement Supérieur et de la Recherche”.

Compliance with ethical standards

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Audrey Berthe
    • 1
  • Marie Zaffino
    • 1
  • Claire Muller
    • 1
  • François Foulquier
    • 2
  • Marine Houdou
    • 2
  • Céline Schulz
    • 2
  • Frédéric Bost
    • 3
    • 4
  • Elia De Fay
    • 1
  • Sabine Mazerbourg
    • 1
    Email author
  • Stéphane Flament
    • 1
  1. 1.Université de Lorraine, CNRS, CRANNancyFrance
  2. 2.Université de Lille, CNRS, UMR 8576 – UGSF - Unité de Glycobiologie Structurale et FonctionnelleLilleFrance
  3. 3.Inserm U1065, Centre Méditerranéen de Médecine Moléculaire, Team “Targeting Prostate Cancer cell metabolism”NiceFrance
  4. 4.Faculty of MedicineUniversité de Nice Sophia-AntipolisNiceFrance

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