Ferroptosis, a new form of cell death: opportunities and challenges in cancer

Journal of Hematology & Oncology, Journal Year: 2019, Volume and Issue: 12(1)

Published: March 29, 2019

Ferroptosis is a novel type of cell death with distinct properties and recognizing functions involved in physical conditions or various diseases including cancers. The fast-growing studies ferroptosis cancer have boosted perspective for its usage therapeutics. Here, we review the current findings regulation especially focus on function ncRNAs mediating process ferroptotic how was relation to other regulated deaths. Aberrant diverse types tissues were summarized, elaborated recent data about actors some "conventional" drugs natural compounds as inducers cancer. Finally, deliberate future orientation cells unsettled issues, which may forward speed clinical use induction treatment.

Language: Английский

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FTH1 Inhibits Ferroptosis Through Ferritinophagy in the 6-OHDA Model of Parkinson's Disease

Neurotherapeutics, Journal Year: 2020, Volume and Issue: 17(4), P. 1796 - 1812

Published: Sept. 21, 2020

Language: Английский

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Arsenic induces pancreatic dysfunction and ferroptosis via mitochondrial ROS-autophagy-lysosomal pathway

Journal of Hazardous Materials, Journal Year: 2019, Volume and Issue: 384, P. 121390 - 121390

Published: Oct. 5, 2019

Language: Английский

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Artesunate alleviates liver fibrosis by regulating ferroptosis signaling pathway

Biomedicine & Pharmacotherapy, Journal Year: 2018, Volume and Issue: 109, P. 2043 - 2053

Published: Nov. 26, 2018

Liver fibrosis is a progression of chronic liver disease, which lacks effective therapies in the world. Attractively, more and evidences show that natural products are safe prevention treatment hepatic fibrosis. Artesunate, water-soluble hemisuccinate derivative artemisinin, exerts various pharmacological activities such as anti-inflammatory, anti-tumor immunomodulating abilities. However, effects artesunate on little-known. Here our study was performed to investigate effect carbon tetrachloride (CCl4)-induced mouse elucidate whether could alleviate by regulating ferritinophagy- mediated ferroptosis stellate cells (HSCs). Firstly, results demonstrated induce activated HSC fibrotic livers. Moreover, primary HSCs isolated from different animal groups were cultured detect biomarkers including iron, lipid peroxidation, glutathione (GSH) prostaglandin endoperoxide synthase 2 (ptgs2) levels. The revealed remarkably promoted HSCs. Furthermore, consistent with experimental vivo, data vitro still indicated markedly induced HSCs, mainly embodied declined cell vitality, increased death rate, accumulated elevated peroxides reduced antioxidant capacity. Conversely, inhibition deferoxamine (DFO) completely abolished artesunate-induced anti-fibrosis effect. Surprisingly, also evidently triggered ferritinophagy accompanied up-regulation LC3 (microtubule-associated protein light chain 3), Atg3, Atg5, Atg6/beclin1, Atg12 (autophagy related genes) down-regulation p62, FTH1 (ferritin heavy chain), NCOA4 (nuclear receptor co-activator 4) Nevertheless, depletion specific inhibitor lysosomal lumen alkalizer-chloroquine (CQ) inhibited function. These suggested ferritinophagy-mediated responsible for efficacy, provided new clues further artesunate.

Language: Английский

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The Role of NCOA4-Mediated Ferritinophagy in Health and Disease

Pharmaceuticals, Journal Year: 2018, Volume and Issue: 11(4), P. 114 - 114

Published: Oct. 23, 2018

Nuclear receptor coactivator 4 (NCOA4) is a selective cargo that mediates the autophagic degradation of ferritin (“ferritinophagy”), cytosolic iron storage complex. NCOA4-mediated ferritinophagy maintains intracellular homeostasis by facilitating or release according to demand. Ferritinophagy involved in iron-dependent physiological processes such as erythropoiesis, where NCOA4 for mitochondrial heme synthesis. Recently, has been shown regulate ferroptosis, newly described form cell death mediated excess lipid peroxidation. Dysregulation metabolism and ferroptosis have neurodegeneration, cancer, infection, but little known about role pathogenesis these diseases. Here, we will review biochemical regulation NCOA4, its contribution disease. Finally, discuss potential activating inhibiting therapeutic purposes.

Language: Английский

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Iron Metabolism in Cancer

International Journal of Molecular Sciences, Journal Year: 2018, Volume and Issue: 20(1), P. 95 - 95

Published: Dec. 27, 2018

Demanded as an essential trace element that supports cell growth and basic functions, iron can be harmful cancerogenic though. By exchanging between its different oxidized forms, overload induces free radical formation, lipid peroxidation, DNA, protein damages, leading to carcinogenesis or ferroptosis. Iron also plays profound roles in modulating tumor microenvironment metastasis, maintaining genomic stability controlling epigenetics. order meet the high requirement of iron, neoplastic cells have remodeled metabolism pathways, including acquisition, storage, efflux, which makes manipulating homeostasis a considerable approach for cancer therapy. Several chelators oxide nanoparticles (IONPs) has recently been developed intervention presented effects. This review summarizes some latest findings about function regulation mechanism application IONPs diagnosis

Language: Английский

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Iron dyshomeostasis, lipid peroxidation and perturbed expression of cystine/glutamate antiporter in Alzheimer’s disease: Evidence of ferroptosis

Redox Biology, Journal Year: 2020, Volume and Issue: 32, P. 101494 - 101494

Published: March 6, 2020

Iron dyshomeostasis is implicated in Alzheimer's disease (AD) alongside β-amyloid and tau pathologies. Despite the recent discovery of ferroptosis, an iron-dependent form cell death, hitherto, vivo evidence ferroptosis AD lacking. The present study uniquely adopts integrated multi-disciplinary approach, combining protein (Western blot) elemental analysis (total reflection X-ray fluorescence) with metabolomics (1H nuclear magnetic resonance spectroscopy) to identify iron possible novel interactions metabolic dysfunction age-matched male cognitively normal (CN) post-mortem brain tissue (n = 7/group). Statistical was used compute differences between CN AD, examine associations proteins, elements and/or metabolites. elevated levels ferritin, absence increased iron, observed AD. Moreover, characterised by enhanced expression light-chain subunit cystine/glutamate transporter (xCT) lipid peroxidation, reminiscent augmented excitatory glutamate inhibitory GABA ratio. Protein, element metabolite also greatly differed suggesting widespread dysregulation We demonstrate dyshomeostasis, upregulated xCT (impaired glutathione metabolism) peroxidation anti-ferroptotic therapies may be efficacious

Language: Английский

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PM2.5 induces ferroptosis in human endothelial cells through iron overload and redox imbalance

Environmental Pollution, Journal Year: 2019, Volume and Issue: 254, P. 112937 - 112937

Published: July 30, 2019

Language: Английский

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The interaction between ferroptosis and inflammatory signaling pathways

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(3)

Published: March 21, 2023

Abstract Ferroptosis is an iron-dependent regulated cell death driven by excessive lipid peroxidation. Inflammation one common and effective physiological event that protects against various stimuli to maintain tissue homeostasis. However, the dysregulation of inflammatory responses can cause imbalance immune system, dysfunction death. Recent studies have pointed out activation inflammation, including multiple inflammation-related signaling pathways, lead ferroptosis. Among related signal transduction we focused on five classical namely, JAK-STAT, NF-κB, inflammasome, cGAS-STING MAPK expounded their roles in To date, many agents shown therapeutic effects ferroptosis-related diseases modulating aforementioned pathways vivo vitro. Moreover, regulatory these iron metabolism peroxidation been described detail, contributing further understanding pathophysiological process Taken together, targeting inflammation will provide appropriate ways intervene ferroptosis diseases.

Language: Английский

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Iron Metabolism, Ferroptosis, and the Links With Alzheimer’s Disease

Frontiers in Neuroscience, Journal Year: 2020, Volume and Issue: 13

Published: Jan. 29, 2020

Iron is an essential transition metal for numerous biologic processes in mammals. metabolism and homeostasis are regulated via several coordination mechanisms including absorption, utilization, recycling, storage.Iron dyshomeostasis can result intracellular excessive iron accumulation,thereby damaging cells, tissues organs through free oxygen radicals generation. Numerous studies have showed that overload of brain involved the pathological mechanism Alzheimer's disease.However,the underlying not been fully elucidated. Ferroptosis , a newly defined iron-dependent form cell death, which distinct from apoptosis, necrosis, autophagy other forms death,may provide us new viewpoints. Here, we summarizes current knowledge ferroptosis, reviews contributions ferroptosis disease.

Language: Английский

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