The Interrelationship of Pharmacologic Ascorbate Induced Cell Death and Ferroptosis

Tamás Lőrincz, Marianna Holczer, Orsolya Kapuy, András Szarka

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)669-679
Number of pages11
JournalPathology and Oncology Research
Volume25
Issue number2
DOIs
Publication statusPublished - Apr 15 2019

Keywords

  • Cell death
  • Ferroptosis
  • Lipid peroxidation
  • Pharmacologic ascorbate
  • ROS

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'The Interrelationship of Pharmacologic Ascorbate Induced Cell Death and Ferroptosis'. Together they form a unique fingerprint.

  • Cite this