Superoxide-mediated ferroptosis in human cancer cells induced by sodium selenite

Karthikeyan Subburayan, Faisal Thayyullathil, Siraj Pallichankandy, Anees Rahman Cheratta, Sehamuddin Galadari

Research output: Contribution to journalArticlepeer-review

Abstract

Ferroptosis is a novel form of programmed cell death characterized by an iron-dependent increase in reactive oxygen species (ROS). However, the role of ROS in the regulation of ferroptosis remains elusive. In this study, for the first time, we demonstrate that sodium selenite (SS), a well-established redox-active selenium compound, is a novel inducer of ferroptosis in a variety of human cancer cells. Potent ferroptosis inhibitors, such as ferrostatin-1 (Fer-1) and deferoxamine (DFO), rescue cells from SS-induced ferroptosis. Furthermore, SS down-regulates ferroptosis regulators; solute carrier family 7 member 11 (SLC7A11), glutathione (GSH), and glutathione peroxidase 4 (GPx4), while it up-regulates iron accumulation and lipid peroxidation (LPO). These SS-induced ferroptotic responses are achieved via ROS, in particular superoxide (O2[rad]) generation. Antioxidants such as superoxide dismutase (SOD) and Tiron not only scavenged O2[rad] production, but also markedly rescued SLC7A11 down-regulation, GSH depletion, GPx4 inactivation, iron accumulation, LPO, and ferroptosis. Moreover, iron chelator DFO significantly reduces the O2[rad] production, indicating a positive feedback regulation between O2[rad] production and iron accumulation. Taken together, we have identified SS as a novel ferroptosis inducing agent in various human cancer models.

Original languageEnglish (US)
Article number100843
JournalTranslational Oncology
Volume13
Issue number11
DOIs
StatePublished - Nov 2020

Keywords

  • Deferoxamine
  • Ferroptosis
  • Ferrostatin-1
  • Lipid peroxidation
  • ROS
  • Sodium selenite

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Superoxide-mediated ferroptosis in human cancer cells induced by sodium selenite'. Together they form a unique fingerprint.

Cite this