The roles of ferroptosis in cancer: Tumor suppression, tumor microenvironment, and therapeutic interventions

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(4), P. 513 - 534

Published: April 1, 2024

Language: Английский

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Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 14, 2024

Iron, an essential mineral in the body, is involved numerous physiological processes, making maintenance of iron homeostasis crucial for overall health. Both overload and deficiency can cause various disorders human diseases. Ferroptosis, a form cell death dependent on iron, characterized by extensive peroxidation lipids. Unlike other kinds classical unprogrammed death, ferroptosis primarily linked to disruptions metabolism, lipid peroxidation, antioxidant system imbalance. Ferroptosis regulated through transcription, translation, post-translational modifications, which affect cellular sensitivity ferroptosis. Over past decade or so, diseases have been as part their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous cardiovascular musculoskeletal Ferroptosis-related proteins become attractive targets many major that are currently incurable, some regulators shown therapeutic effects clinical trials although further validation potential needed. Therefore, in-depth analysis its molecular mechanisms may offer additional strategies prevention treatment. In this review, we discuss significance contribution etiology development along with evidence supporting targeting approach. Importantly, evaluate recent promising interventions, providing guidance future targeted treatment therapies against

Language: Английский

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Ferroptosis: principles and significance in health and disease

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: June 6, 2024

Abstract Ferroptosis, an iron-dependent form of cell death characterized by uncontrolled lipid peroxidation, is governed molecular networks involving diverse molecules and organelles. Since its recognition as a non-apoptotic pathway in 2012, ferroptosis has emerged crucial mechanism numerous physiological pathological contexts, leading to significant therapeutic advancements across wide range diseases. This review summarizes the fundamental mechanisms regulatory pathways underlying ferroptosis, including both GPX4-dependent -independent antioxidant mechanisms. Additionally, we examine involvement various conditions, cancer, neurodegenerative diseases, sepsis, ischemia–reperfusion injury, autoimmune disorders, metabolic disorders. Specifically, explore role response chemotherapy, radiotherapy, immunotherapy, nanotherapy, targeted therapy. Furthermore, discuss pharmacological strategies for modulating potential biomarkers monitoring this process. Lastly, elucidate interplay between other forms regulated death. Such insights hold promise advancing our understanding context human health disease.

Language: Английский

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STING orchestrates the neuronal inflammatory stress response in multiple sclerosis

Cell, Journal Year: 2024, Volume and Issue: 187(15), P. 4043 - 4060.e30

Published: June 14, 2024

Inflammation-induced neurodegeneration is a defining feature of multiple sclerosis (MS), yet the underlying mechanisms remain unclear. By dissecting neuronal inflammatory stress response, we discovered that neurons in MS and its mouse model induce stimulator interferon genes (STING). However, activation STING requires detachment from stromal interaction molecule 1 (STIM1), process triggered by glutamate excitotoxicity. This initiates non-canonical signaling, which leads to autophagic degradation glutathione peroxidase 4 (GPX4), essential for redox homeostasis thereby inducing ferroptosis. Both genetic pharmacological interventions target protect against inflammation-induced neurodegeneration. Our findings position as central regulator detrimental integrating inflammation with signaling cause cell death, present it tractable treating MS.

Language: Английский

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Breast cancer: pathogenesis and treatments

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 18, 2025

Abstract Breast cancer, characterized by unique epidemiological patterns and significant heterogeneity, remains one of the leading causes malignancy-related deaths in women. The increasingly nuanced molecular subtypes breast cancer have enhanced comprehension precision treatment this disease. mechanisms tumorigenesis progression been central to scientific research, with investigations spanning various perspectives such as tumor stemness, intra-tumoral microbiota, circadian rhythms. Technological advancements, particularly those integrated artificial intelligence, significantly improved accuracy detection diagnosis. emergence novel therapeutic concepts drugs represents a paradigm shift towards personalized medicine. Evidence suggests that optimal diagnosis models tailored individual patient risk expected are crucial, supporting era oncology for cancer. Despite rapid advancements increasing emphasis on clinical comprehensive update summary panoramic knowledge related disease needed. In review, we provide thorough overview global status including its epidemiology, factors, pathophysiology, subtyping. Additionally, elaborate latest research into contributing progression, emerging strategies, long-term management. This review offers valuable insights Cancer Research, thereby facilitating future progress both basic application.

Language: Английский

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Machine learning with label-free Raman microscopy to investigate ferroptosis in comparison with apoptosis and necroptosis

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Feb. 11, 2025

Human and animal health rely on balancing cell division death to maintain normal homeostasis. This process is accomplished by regulated (RCD), whose imbalance can lead disease. Currently, the most frequently used method for analyzing RCD fluorescence microscopy. has limitations potential side effects due presence of fluorescent labels. Furthermore, often lacks specificity may have effects. In quest overcome such difficulties, label-free approaches come into focus.Here, Raman microscopy in combination with machine learning investigate RCDs, where biochemical molecular "fingerprints" are investigated a focus vibrations atoms molecules. Three different unique types genetic machinery, namely, ferroptosis studied comparison apoptosis, necroptosis murine fibroblast line L929sAhFas. Interestingly, during ferroptosis, decrease wavenumber at 939 cm-1 was observed, which associated reduction expression collagen – compound essential multiple diseases. Data analysis performed (ML), here SVMs, model utilizing spectra directly support vector (SVM) outperforms other SVM strategies correctly predicting 73% all spectra. Other methods: PCA-SVM (principal component analysis-SVM), peak fitting-AUC-SVM (area under curve) fitting-spectral reconstruction-SVM rendered prediction accuracies ~52%, ~43%, 61%, respectively. Peak fitting additional benefit enabling biological interpretation scattering peaks using area curve, although loss general accuracy. The biology, pipelines, be applied broader field not limited death. Verduijn et al show that modalities. allows investigation apoptosis necroptosis.

Language: Английский

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In defence of ferroptosis

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 2, 2025

Abstract Rampant phospholipid peroxidation initiated by iron causes ferroptosis unless this is restrained cellular defences. Ferroptosis increasingly implicated in a host of diseases, and unlike other cell death programs the physiological initiation conceived to occur not an endogenous executioner, but withdrawal guardians that otherwise constantly oppose induction. Here, we profile key ferroptotic defence strategies including regulation, modulation enzymes metabolite systems: glutathione reductase (GR), suppressor protein 1 (FSP1), NAD(P)H Quinone Dehydrogenase (NQO1), Dihydrofolate (DHFR), retinal reductases dehydrogenases (RDH) thioredoxin (TR). A common thread uniting all metabolites combat lipid during dependence on reductant, nicotinamide adenine dinucleotide phosphate (NADPH). We will outline how cells control central carbon metabolism produce NADPH necessary precursors defend against ferroptosis. Subsequently discuss evidence for dysregulation different disease contexts glucose-6-phosphate dehydrogenase deficiency, cancer neurodegeneration. Finally, several anti-ferroptosis therapeutic spanning use radical trapping agents, dependent redox support highlight current landscape clinical trials focusing

Language: Английский

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Metal Ion Signaling in Biomedicine

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Complex multicellular organisms are composed of distinct tissues involving specialized cells that can perform specific functions, making such life forms possible. Species defined by their genomes, and differences between individuals within a given species directly result from variations in genetic codes. While alterations give rise to disease-causing acquisitions cell identities, it is now well-established biochemical imbalances also lead cellular dysfunction diseases. Specifically, nongenetic chemical events orchestrate metabolism transcriptional programs govern functional identity. Thus, signaling, which broadly defines the conversion extracellular signals into intracellular changes, contribute acquisition diseased states. Metal ions exhibit unique properties be exploited cell. For instance, metal maintain ionic balance cell, coordinate amino acid residues or nucleobases altering folding function biomolecules, catalyze reactions. metals essential signaling effectors normal physiology disease. Deciphering ion challenging endeavor illuminate pathways targeted for therapeutic intervention. Here, we review key processes where play roles describe how targeting has been instrumental dissecting biochemistry this led development effective strategies.

Language: Английский

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Mechanisms of Ferroptosis in bone disease: A new target for osteoporosis treatment

Cellular Signalling, Journal Year: 2025, Volume and Issue: 127, P. 111598 - 111598

Published: Jan. 7, 2025

Language: Английский

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FSP1-mediated lipid droplet quality control prevents neutral lipid peroxidation and ferroptosis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

ABSTRACT Lipid droplets (LDs) are organelles that store and supply lipids based on cellular needs. While mechanisms preventing oxidative damage to membrane phospholipids established, the vulnerability of LD neutral peroxidation protective unknown. Here, we identify LD-localized Ferroptosis Suppressor Protein 1 (FSP1) as a critical regulator prevents lipid by recycling coenzyme Q10 (CoQ10) its lipophilic antioxidant form. Lipidomics reveal FSP1 loss leads accumulation oxidized triacylglycerols cholesteryl esters, biochemical reconstitution with CoQ10 NADH suppresses triacylglycerol in vitro . Notably, polyunsaturated fatty acid (PUFA)-rich enhance cancer cell sensitivity inducing PUFA-rich LDs triggers LD-initiated ferroptosis when activity is impaired. These findings uncover first quality control pathway, wherein maintains integrity prevent buildup induction ferroptosis.

Language: Английский

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