Targeting Nrf2 for ferroptosis-based therapy: Implications for overcoming ferroptosis evasion and therapy resistance in cancer

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2023, Номер 1869(7), С. 166788 - 166788

Опубликована: Июнь 10, 2023

Язык: Английский

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Molecular Mechanisms of Ferroptosis and Updates of Ferroptosis Studies in Cancers and Leukemia

Cells, Год журнала: 2023, Номер 12(8), С. 1128 - 1128

Опубликована: Апрель 11, 2023

Ferroptosis is a mode of cell death regulated by iron-dependent lipid peroxidation. Growing evidence suggests ferroptosis induction as novel anti-cancer modality that could potentially overcome therapy resistance in cancers. The molecular mechanisms involved the regulation are complex and highly dependent on context. Therefore, comprehensive understanding its execution protection machinery each tumor type necessary for implementation this unique to target individual Since most current based solid cancer studies, knowledge with regard leukemia largely lacking. In review, we summarize ferroptosis-regulating respect metabolism phospholipids iron well major anti-oxidative pathways protect cells from ferroptosis. We also highlight diverse impact p53, master regulator cellular metabolic processes, Lastly, discuss recent studies provide future perspective development promising anti-leukemia therapies implementing induction.

Язык: Английский

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Selenoprotein P expression in glioblastoma as a regulator of ferroptosis sensitivity: preservation of GPX4 via the cycling-selenium storage

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Янв. 5, 2024

Abstract Glioblastoma (GBM) is one of the most aggressive and deadly brain tumors; however, its current therapeutic strategies are limited. Selenoprotein P (SeP; SELENOP, encoded by SELENOP gene) a unique selenium-containing protein that exhibits high expression levels in astroglia. SeP thought to be associated with ferroptosis sensitivity through induction glutathione peroxidase 4 (GPX4) via selenium supplementation. In this study, elucidate role GBM, we analyzed GBM patients found were significantly higher when compared healthy subjects. Knock down cultured cells resulted decrease GPX1 GPX4 levels. Under same conditions, cell death caused RSL3, inducer, was enhanced, however enhancement canceled supplementation selenite. These results indicate contributes preserving GPX an autocrine/paracrine manner, i.e., regulates dynamic cycling-selenium storage system GBM. We also confirmed using patient-derived primary cells. findings can significant target overcome anticancer drug resistance.

Язык: Английский

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Ferroptosis and EMT resistance in cancer: a comprehensive review of the interplay

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Фев. 26, 2024

Ferroptosis differs from traditional cell death mechanisms like apoptosis, necrosis, and autophagy, primarily due to its reliance on iron metabolism the loss of glutathione peroxidase activity, leading lipid peroxidation death. The dysregulation is a hallmark various cancers, contributing tumor progression, metastasis, notably, drug resistance. acquisition mesenchymal characteristics by epithelial cells known as Epithelial–Mesenchymal Transition (EMT), biological process intricately linked cancer development, promoting traits such invasiveness, resistance therapeutic interventions. EMT plays pivotal role in progression contributes significantly complex dynamics carcinogenesis. Research findings indicate that exhibit greater susceptibility ferroptosis compared their counterparts. induction becomes more effective eliminating drug-resistant during EMT. interplay between EMT, where transform into mobile cells, crucial understanding progression. associated with increased metastasis review delves how influence each other, highlighting key proteins GPX4, which protects against peroxidation, inhibition can induce ferroptosis. Conversely, GPX4 expression heightened cells. Moreover, discusses implications EMT-induced transcription factors Snail, Zeb1, Twist modulating sensitivity ferroptosis, thereby affecting treatment outcomes. Targeting pathway offers promising strategy, particularly for tumors resistant conventional treatments. these could potentially overcome However, translating clinical practice presents challenges, including precise induction, identifying predictive biomarkers, optimizing combination therapies. underscores need further research unravel interactions cancer. This lead development effective, targeted treatments, tumors, offering new hope therapeutics.

Язык: Английский

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Diethyldithiocarbamate-ferrous oxide nanoparticles inhibit human and mouse glioblastoma stemness: aldehyde dehydrogenase 1A1 suppression and ferroptosis induction

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Апрель 24, 2024

The development of effective therapy for eradicating glioblastoma stem cells remains a major challenge due to their aggressive growth, chemoresistance and radioresistance which are mainly conferred by aldehyde dehydrogenase (ALDH)1A1. latter is the main stemness mediator via enhancing signaling pathways Wnt/β-catenin, phosphatidylinositol 3-kinase/AKT, hypoxia. Furthermore, ALDH1A1 mediates therapeutic resistance inactivating drugs, stimulating expression drug efflux transporters, detoxifying reactive radical species, thereby apoptosis arresting. Recent reports disclosed potent broad-spectrum anticancer activities unique nanocomplexes diethyldithiocarbamate (DE, inhibitor) with ferrous oxide nanoparticles (FeO NPs) inducing lipid peroxidation-dependent non-apoptotic (iron accumulation-triggered ferroptosis), was reported. Accordingly, anti-stemness activity (DE-FeO investigated against human mouse glioma (GSCs) radioresistant GSCs (GSCs-RR). DE-FeO NPs exhibited strongest growth inhibition effect on treated (MGG18 JX39P), (GS PDGF-GSC) (IC 50 ≤ 70 161 μg/mL, respectively). also revealed higher inhibitory impact than standard chemotherapy (temozolomide, TMZ) self-renewal, cancer repopulation, chemoresistance, potentials. Besides, surpassed TMZ regarding relative all studied genes, as well p-AKT/AKT ratio in MGG18, GS (MGG18-RR GS-RR). This influence primarily attributed ferroptosis induction, confirmed significant elevation cellular oxygen species peroxidation depletion glutathione peroxidase 4. recorded optimal Log P value crossing blood brain barrier. vitro novel study declared potency collapsing GSCs-RR improving sensitivity radiotherapy, indicating that may be promising remedy GBM. Glioma animal models will needed in-depth studies its safe effectiveness.

Язык: Английский

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Competing endogenous RNA networks and ferroptosis in cancer: novel therapeutic targets

Cell Death and Disease, Год журнала: 2024, Номер 15(5)

Опубликована: Май 22, 2024

Abstract As a newly identified regulated cell death, ferroptosis is metabolically driven process that relies on iron and associated with polyunsaturated fatty acyl peroxidation, elevated levels of reactive oxygen species (ROS), mitochondrial damage. This distinct death dysregulated in various cancers; activating malignant cells increases cancer immunotherapy chemoradiotherapy responses across different malignancies. Over the last decade, accumulating research has provided evidence cross-talk between non-coding RNAs (ncRNAs) competing endogenous RNA (ceRNA) networks highlighted their significance developing progressing Aside from pharmaceutical agents to regulate ferroptosis, recent studies have shed light potential restoring ferroptosis-related ceRNA treatment. The present study provides comprehensive up-to-date review significance, pathways, role chemoradiotherapy, biogenesis, ferroptosis-regulating cancers. insights can offer authorship state-of-the-art findings future perspectives regarding implication treatment determining prognosis affected patients.

Язык: Английский

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Copper ions induces ferroptosis in Staphylococcus aureus and promotes healing of MRSA-induced wound infections

Microbiological Research, Год журнала: 2025, Номер 296, С. 128122 - 128122

Опубликована: Фев. 26, 2025

Язык: Английский

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The Roles of DMT1 in Inflammatory and Degenerative Diseases

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Язык: Английский

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From mechanisms to medicine: Ferroptosis as a Therapeutic target in liver disorders

Cell Communication and Signaling, Год журнала: 2025, Номер 23(1)

Опубликована: Март 7, 2025

In recent 10 years, ferroptosis has become a hot research direction in the scientific community as new way of cell death. Iron toxicity accumulation and lipotoxicity are unique features. Several studies have found that is involved regulation hepatic microenvironment various metabolisms, thereby mediating progression related liver diseases. For example, NRF2 FSP1, important regulatory proteins ferroptosis, development tumors failure. this manuscript, we present mechanisms concern with addition, summarize clinical advances targeted therapy for We expect manuscript can provide perspective treatment

Язык: Английский

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The Regulation of Trace Metal Elements in Cancer Ferroptosis

Advanced Biology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 9, 2025

Abstract Ferroptosis, as novel type of regulated cell death that has garnered widespread attention over the past decade, witnessed continuous discovery an increasing number regulatory mechanisms. Trace metal elements play a multifaceted and crucial role in oncology. Interestingly, it been increasingly evident these elements, such copper, are involved regulation iron accumulation, lipid peroxidation antiferroptotic systems, suggesting existence “nonferrous” mechanisms ferroptosis. In this review, comprehensive overview composition mechanism ferroptosis is provided. The interaction between copper metabolism (including cuproptosis) cancer, well roles other trace (such zinc, manganese, cobalt, molybdenum) specifically focused. Furthermore, applications nanomaterials based on metals cancer therapy also reviewed potential strategies for co‐targeting cuproptosis explored. Nevertheless, light intricate ambiguous nature interactions, ongoing research essential to further elucidate ferroptosis, thereby facilitating development therapeutic targets approaches treatment.

Язык: Английский

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