Superoxide-mediated ferroptosis in human cancer cells induced by sodium selenite
| Autor: | Siraj Pallichankandy, Faisal Thayyullathil, Anees Rahman Cheratta, Sehamuddin Galadari, Karthikeyan Subburayan |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research NSA necrosulfonamide GSH reduced glutathione MLKL mixed lineage kinase domain-like CO2 carbon dioxide DMSO dimethyl sulfoxide MTT 3-[4 5-dimethylthiazol-2-yl]-2 5-diphenyl tetrazolium bromide GPX4 DCFH-DA 2′ 7′-dichlorodihydrofluorescein diacetate DTNB 5 5′-dithiobis-(2-nitrobenzoic acid) Ferrostatin-1 Lipid peroxidation chemistry.chemical_compound Fer-1 ferrostatin-1 0302 clinical medicine RIPK1 receptor interacting protein kinase 1 RIPK3 receptor interacting protein kinase 3 PCD programmed cell death Sodium selenite BafA1 bafilomycinA1 PARP poly ADP-ribose polymerase chemistry.chemical_classification biology EDTA ethylene diamine tetra acetic acid SLC7A11 solute carrier family 7 member 11 Superoxide ROS lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens DFO deferoxamine mesylate Cell biology NADPH membrane nicotinamide adenine dinucleotide phosphate Deferoxamine Oncology FoxO3a Forkhead box O3 H2O2 hydrogen peroxide 030220 oncology & carcinogenesis GPx4 glutathione peroxidase 4 LPO lipid peroxidation Bim Bcl-2-like protein NPC nutritional prevention of cancer medicine.drug Original article RCD regulated cell death FIN56 ferroptosis inducing compound 56 AKT protein kinase B lcsh:RC254-282 NaPy sodium pyruvate Superoxide dismutase 03 medical and health sciences FBS fetal bovine serum PBS phosphate buffered saline SOD superoxide dismutase CHP cumene hydroperoxide medicine Ferroptosis 3MA 3-methyl adenine RSL3 RAS-selective lethal 3 z-VAD-FMK Benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone SNG sanguinarine Tiron Reactive oxygen species ROS reactive oxygen species generation Nec-1 necrostatin-1 DPI diphenylene iodonium chloride FeCl3 ferric chloride HCQ hydroxychloroquine Glutathione PTEN phosphatase and tensin homolog 030104 developmental biology chemistry NAC N-acetyl cysteine biology.protein DHE dihydroethidium |
| Zdroj: | Translational Oncology, Vol 13, Iss 11, Pp 100843-(2020) Translational Oncology |
| ISSN: | 1936-5233 |
| DOI: | 10.1016/j.tranon.2020.100843 |
| Popis: | 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•−) generation. Antioxidants such as superoxide dismutase (SOD) and Tiron not only scavenged O2•− 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•− production, indicating a positive feedback regulation between O2•− production and iron accumulation. Taken together, we have identified SS as a novel ferroptosis inducing agent in various human cancer models. Graphical abstract Unlabelled Image Highlights • Sodium selenite selectively induces ferroptosis in multiple human cancer cells. • Sodium selenite inhibits system Xc− function and altered GSH homeostasis. • Superoxide is the ROS molecule responsible for the sodium selenite-induced ferroptosis. • Sodium selenite induces iron accumulation via superoxide dependent mechanism. |
| Databáze: | OpenAIRE |
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