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Pathology & Oncology Research

, Volume 25, Issue 2, pp 669–679 | Cite as

The Interrelationship of Pharmacologic Ascorbate Induced Cell Death and Ferroptosis

  • Tamás Lőrincz
  • Marianna Holczer
  • Orsolya Kapuy
  • András SzarkaEmail author
Original Article
  • 264 Downloads

Abstract

Pharmacologic ascorbate induced cell death and ferroptosis share common features such as iron dependency, production of ROS, lipid peroxidation, caspase independency and the possible involvement of autophagy. These observations lead us to hypothesize that ferroptosis may also be involved in cancer cell death due to pharmacologic ascorbate treatment. Thus cell death of HT-1080 cell line was induced by ferroptosis inducers and pharmacologic ascorbate then the mechanism of cell death was compared. The EC50 value of pharmacologic ascorbate on HT-1080 cell line was found to be 0.5 mM that is in the range of the most ascorbate sensitive cell lines. However either of the specific inhibitors of ferroptosis (ferrostatin-1 and liproxstatin-1) could not elevate the viability of pharmacologic ascorbate treated cells suggesting that ferroptosis was not involved in the pharmacologic ascorbate induced cell death. α-tocopherol that could effectively elevate the viability of erastin and RSL3 treated HT1080 cells failed to mitigate the cytotoxic effect of pharmacologic ascorbate further strengthened this assumption. Furthermore at lower concentrations (0.1–0.5 mM) ascorbate could avoid the effects of ferroptosis inducers. Our results indicate that pharmacologic ascorbate induced cytotoxicity and ferroptosis – albeit phenotypically they show similar traits – are governed by different mechanisms.

Keywords

Pharmacologic ascorbate Cell death ROS Lipid peroxidation Ferroptosis 

Notes

Acknowledgements

We acknowledge Dr. Anita Sebestyén, of Semmelweis University Budapest for her generous gift of the HT-1080 cell line and Pál Gyulavári for his kind assistance for the FACSCalibur™ flow cytometer.

Funding

This work was financially supported by the National Research, Development and Innovation Fund of Hungary under Grant K 123752, 129593 by the BME-Biotechnology FIKP grant of EMMI and MedinProt Protein Excellence foundation.

Compliance with Ethical Standards

Conflicts of Interest

The authors declare no conflict of interest.

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Copyright information

© Arányi Lajos Foundation 2018

Authors and Affiliations

  1. 1.Department of Applied Biotechnology and Food Science, Laboratory of Biochemistry and Molecular BiologyBudapest University of Technology and EconomicsBudapestHungary
  2. 2.Department of Medical Chemistry, Molecular Biology and PathobiochemistrySemmelweis UniversityBudapestHungary
  3. 3.Pathobiochemistry Research Group of Hungarian Academy of Sciences and Semmelweis UniversityBudapestHungary

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