Ferroptosis: past, present and future

Cell Death and Disease, Journal Year: 2020, Volume and Issue: 11(2)

Published: Feb. 3, 2020

Abstract Ferroptosis is a new type of cell death that was discovered in recent years and usually accompanied by large amount iron accumulation lipid peroxidation during the process; occurrence ferroptosis iron-dependent. Ferroptosis-inducing factors can directly or indirectly affect glutathione peroxidase through different pathways, resulting decrease antioxidant capacity reactive oxygen species (ROS) cells, ultimately leading to oxidative death. Recent studies have shown closely related pathophysiological processes many diseases, such as tumors, nervous system ischemia-reperfusion injury, kidney blood diseases. How intervene development diseases regulating has become hotspot focus etiological research treatment, but functional changes specific molecular mechanisms still need be further explored. This paper systematically summarizes latest progress research, with on providing references for understanding its pathogenesis proposing targets treatment

Language: Английский

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Targeting ferroptosis as a vulnerability in cancer

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(7), P. 381 - 396

Published: March 25, 2022

Language: Английский

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Ferroptosis: machinery and regulation

Autophagy, Journal Year: 2020, Volume and Issue: 17(9), P. 2054 - 2081

Published: Aug. 19, 2020

Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death caused by lipid peroxidation, which controlled integrated oxidation and antioxidant systems. The iron-containing enzyme lipoxygenase the main promoter ferroptosis producing hydroperoxides, its function relies on activation ACSL4-dependent biosynthesis. In contrast, selenium-containing GPX4 currently recognized as a central repressor ferroptosis, activity depends glutathione produced from cystine-glutamate antiporter SLC7A11. Many metabolic (especially involving iron, lipids, amino acids) degradation pathways (macroautophagy/autophagy ubiquitin-proteasome system) orchestrate complex ferroptotic response through direct or indirect regulation iron accumulation peroxidation. Although detailed mechanism membrane injury during remains mystery, ESCRT III-mediated plasma repair can make cells resistant to ferroptosis. Here, we review recent rapid progress in understanding molecular mechanisms focus epigenetic, transcriptional, posttranslational this process.Abbreviations: 2ME: beta-mercaptoethanol; α-KG: α-ketoglutarate; ccRCC: clear renal carcinoma; EMT: epithelial-mesenchymal transition; FAO: fatty acid beta-oxidation; GSH: glutathione; MEFs: mouse embryonic fibroblasts; MUFAs: monounsaturated acids; NO: nitric oxide; NOX: NADPH oxidase; PPP: pentose phosphate pathway; PUFA: polyunsaturated acid; RCD: death; RNS: reactive nitrogen species; ROS: oxygen RTAs: radical-trapping antioxidants; UPS: system; UTR: untranslated region.

Language: Английский

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Ferroptosis: mechanisms and links with diseases

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Feb. 3, 2021

Abstract Ferroptosis is an iron-dependent cell death, which different from apoptosis, necrosis, autophagy, and other forms of death. The process ferroptotic death defined by the accumulation lethal lipid species derived peroxidation lipids, can be prevented iron chelators (e.g., deferiprone, deferoxamine) small lipophilic antioxidants ferrostatin, liproxstatin). This review summarizes current knowledge about regulatory mechanism ferroptosis its association with several pathways, including iron, lipid, cysteine metabolism. We have further discussed contribution to pathogenesis diseases such as cancer, ischemia/reperfusion, various neurodegenerative Alzheimer’s disease Parkinson’s disease), evaluated therapeutic applications inhibitors in clinics.

Language: Английский

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Ferroptosis in cancer therapy: a novel approach to reversing drug resistance

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Feb. 12, 2022

Abstract Ferroptosis is an intracellular iron-dependent form of cell death that distinct from apoptosis, necrosis, and autophagy. Extensive studies suggest ferroptosis plays a pivotal role in tumor suppression, thus providing new opportunities for cancer therapy. The development resistance to therapy remains major challenge. A number preclinical clinical have focused on overcoming drug resistance. Intriguingly, has been correlated with resistance, inducing demonstrated reverse Herein, we provide detailed description the mechanisms therapeutic regulating reversing common therapies, such as chemotherapy, targeted immunotherapy. We discuss prospect challenge strategy expect our review could some references further studies.

Language: Английский

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A Novel Ferroptosis-related Gene Signature for Overall Survival Prediction in Patients with Hepatocellular Carcinoma

International Journal of Biological Sciences, Journal Year: 2020, Volume and Issue: 16(13), P. 2430 - 2441

Published: Jan. 1, 2020

Hepatocellular carcinoma (HCC) is a highly heterogeneous disease, which makes the prognostic prediction challenging.Ferroptosis, an iron-dependent form of regulated cell death, can be induced by sorafenib.However, value ferroptosis-related genes in HCC remains to further elucidated.In this study, mRNA expression profiles and corresponding clinical data patients were downloaded from public databases.The least absolute shrinkage selection operator (LASSO) Cox regression model was utilized construct multigene signature TCGA cohort.HCC ICGC cohort used for validation.Our results showed that most (81.7%) differentially expressed between adjacent normal tissues cohort.Twenty-six (DEGs) correlated with overall survival (OS) univariate analysis (all adjusted P< 0.05).A 10-gene constructed stratify into two risk groups.Patients high-risk group significantly reduced OS compared low-risk (P < 0.001 P = cohort).The score independent predictor multivariate analyses (HR> 1, 0.01).Receiver operating characteristic (ROC) curve confirmed signature's predictive capacity.Functional revealed immune-related pathways enriched, immune status different groups.In conclusion, novel gene HCC.Targeting ferroptosis may therapeutic alternative HCC.

Language: Английский

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Recent progress in nanomedicine for enhanced cancer chemotherapy

Theranostics, Journal Year: 2021, Volume and Issue: 11(13), P. 6370 - 6392

Published: Jan. 1, 2021

As one of the most important cancer treatment strategies, conventional chemotherapy has substantial side effects and leads easily to failure. Therefore, exploring developing more efficient methods enhance is an urgently problem that must be solved. With development nanotechnology, nanomedicine showed a good application prospect in improving chemotherapy. In this review, we aim present discussion on significant research progress for enhanced First, increased enrichment drugs tumor tissues relying different targeting ligands promoting tissue penetration are summarized. Second, specific subcellular organelle-targeted discussed. Next, combinational strategies reverse multidrug resistance (MDR) improve effective intracellular concentration therapeutics Furthermore, advantages combination therapy emphasized. Finally, discuss major problems facing therapeutic chemotherapy, propose possible future directions field.

Language: Английский

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Ferroptosis, radiotherapy, and combination therapeutic strategies

Protein & Cell, Journal Year: 2021, Volume and Issue: 12(11), P. 836 - 857

Published: April 23, 2021

Ferroptosis, an iron-dependent form of regulated cell death driven by peroxidative damages polyunsaturated-fatty-acid-containing phospholipids in cellular membranes, has recently been revealed to play important role radiotherapy-induced and tumor suppression, mediate the synergy between radiotherapy immunotherapy. In this review, we summarize known as well putative mechanisms underlying crosstalk ferroptosis, discuss interactions ferroptosis other forms induced radiotherapy, explore combination therapeutic strategies targeting This review will provide frameworks for future investigations cancer therapy.

Language: Английский

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<p>The Role of Erastin in Ferroptosis and Its Prospects in Cancer Therapy</p>

OncoTargets and Therapy, Journal Year: 2020, Volume and Issue: Volume 13, P. 5429 - 5441

Published: June 1, 2020

Abstract: Erastin was initially discovered as a small molecule compound that selectively kills tumor cells expressing ST and RAS V12 later widely investigated an inducer of ferroptosis. Ferroptosis is recently form cell death caused by peroxidation induced the accumulation intracellular lipid reactive oxygen species (L-ROS) in iron-dependent manner. can mediate ferroptosis through variety molecules including cystine-glutamate transport receptor (system X C − ), voltage-dependent anion channel (VDAC), p53. able to enhance sensitivity chemotherapy radiotherapy, suggesting promising future cancer therapy. We hope this review will help better understand role erastin lay foundation for further research development erastin-based therapies future. Keywords: erastin, ferroptosis, system , p53, VDAC,

Language: Английский

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Identification of a small molecule as inducer of ferroptosis and apoptosis through ubiquitination of GPX4 in triple negative breast cancer cells

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: Jan. 20, 2021

Abstract Background TNBC is the most aggressive breast cancer with higher recurrence and mortality rate than other types of cancer. There an urgent need for identification therapeutic agents unique mode action overcoming current challenges in treatment. Methods Different inhibitors were used to study cell death manner DMOCPTL . RNA silencing was evaluate functions GPX4 ferroptosis apoptosis cells EGR1 apoptosis. Immunohistochemical assay tissue microarray investigating correlation TNBC. Computer-aided docking small molecule probe binding GPX4. Results , a derivative natural product parthenolide, exhibited about 15-fold improvement comparing that parent compound PTL cells. The showed anti-TNBC effect mainly by inducing through ubiquitination indicated induced directly protein. To best our knowledge, this first report Moreover, mechanism regulation still obscure. Here, we firstly reveal regulated mitochondria-mediated Compound 13 prodrug effectively inhibited growth tumor prolonged lifespan mice vivo, no obvious toxicity observed. Conclusions These findings revealed novel induce provided up-regulation deserves further studies as lead ultimate discovery effective drug.

Language: Английский

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