Molecular Biology Reports

, Volume 46, Issue 1, pp 1275–1284 | Cite as

The unfolded protein response controls endoplasmic reticulum stress-induced apoptosis of MCF-7 cells via a high dose of vitamin C treatment

  • Peter BoberEmail author
  • Zuzana Tomková
  • Michal Alexovič
  • Ivan Ropovik
  • Ján Sabo
Original Article


Recent in vitro studies have shown that vitamin C (Vit C) with pro-oxidative properties causes cytotoxicity of breast cancer cells by selective oxidative stress. However, the effect of Vit C in itself at different concentration levels on MCF-7 breast cancer cell line after 24 h, has not yet been described. We aimed to examine the effect of Vit C on the viability and signalling response of MCF-7/WT (MCF-7 wild-type) cells that were exposed to various concentrations (0.125–4 mM) of Vit C during 24 h. The cytotoxic effect of Vit C on MCF-7/VitC (MCF-7/WT after added 2 mM Vit C) was observed, resulting in a decrease of cell index after 12 h. Also, the cytotoxicity of Vit C (2 mM) after 24 h was confirmed by flow cytometry, i.e., increase of dead, late apoptotic, and depolarized dead MCF-7/VitC cells compared to MCF-7/WT cells. Moreover, changes in proteomic profile of MCF-7/VitC cells compared to the control group were investigated via label-free quantitative mass spectrometry and post-translational modification. Using bioinformatics assessment (i.e., iPathwayGuide and SPIA R packages), a significantly impacted pathway in MCF-7/VitC was identified, namely the protein processing in endoplasmic reticulum. The semi-quantitative change (log2fold change = 4.5) and autophosphorylation at Thr-446 of protein kinase (PKR) (involved in this pathway) indicates that PKR protein could be responsible for the unfolded protein response and inhibition of the cell translation during endoplasmic reticulum stress, and eventually, for cell apoptosis. These results suggest that increased activity of PKR (Thr-446 autophosphorylation) related to cytotoxic effect of Vit C (2 mM) may cause the MCF-7 cells death.


MCF-7 cells Vitamin C Unfolded protein response Endoplasmic reticulum stress PKR protein 



This work was supported by the Agency of the Slovak Ministry of Education for the Structural Funds of the EU, under project ITMS: 26220220143.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants and/or animals performed by any of the authors.

Supplementary material

11033_2019_4598_MOESM1_ESM.xls (42 kb)
Supplementary material 1 (XLS 42 KB)
11033_2019_4598_MOESM2_ESM.xlsx (184 kb)
Supplementary material 2 (XLSX 184 KB)


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Medical and Clinical Biophysics, Faculty of MedicineUniversity of P.J. Šafárik in KošiceKošiceSlovakia
  2. 2.Department of Pre-school and Elementary Education and Psychology, Faculty of Education, University of PresovPresovSlovakia

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