Interplay of Ferroptosis and Cuproptosis in Cancer: Dissecting Metal-Driven Mechanisms for Therapeutic Potentials

Cancers, Journal Year: 2024, Volume and Issue: 16(3), P. 512 - 512

Published: Jan. 24, 2024

Iron (Fe) and copper (Cu), essential transition metals, play pivotal roles in various cellular processes critical to cancer biology, including cell proliferation, mitochondrial respiration, distant metastases, oxidative stress. The emergence of ferroptosis cuproptosis as distinct forms non-apoptotic death has heightened their significance, particularly connection with these metal ions. While initially studied separately, recent evidence underscores the interdependence cuproptosis. Studies reveal a link between accumulation induction. This interconnected relationship presents promising strategy, especially for addressing refractory cancers marked by drug tolerance. Harnessing toxicity iron clinical settings becomes crucial. Simultaneous targeting cuproptosis, exemplified combination sorafenib elesclomol-Cu, represents an intriguing approach. Strategies mitochondria further enhance precision approaches, providing hope improving treatment outcomes drug-resistant cancers. Moreover, chelators copper-lowering agents established therapeutic modalities exhibits synergy that holds promise augmentation anti-tumor efficacy malignancies. review elaborates on complex interplay underlying mechanisms, explores potential druggable targets both research settings.

Language: Английский

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Antioxidant Systems as Modulators of Ferroptosis: Focus on Transcription Factors

Antioxidants, Journal Year: 2024, Volume and Issue: 13(3), P. 298 - 298

Published: Feb. 28, 2024

Ferroptosis is a type of programmed cell death that differs from apoptosis, autophagy, and necrosis related to several physio-pathological processes, including tumorigenesis, neurodegeneration, senescence, blood diseases, kidney disorders, ischemia–reperfusion injuries. linked iron accumulation, eliciting dysfunction antioxidant systems, which favor the production lipid peroxides, membrane damage, ultimately, death. Thus, signaling pathways evoking ferroptosis are strongly associated with those protecting cells against excess and/or lipid-derived ROS. Here, we discuss interaction between metabolic particular focus on transcription factors implicated in regulation ferroptosis, either as triggers peroxidation or defense pathways.

Language: Английский

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Lipid metabolism disorder in diabetic kidney disease

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: April 29, 2024

Diabetic kidney disease (DKD), a significant complication associated with diabetes mellitus, presents limited treatment options. The progression of DKD is marked by substantial lipid disturbances, including alterations in triglycerides, cholesterol, sphingolipids, phospholipids, droplets, and bile acids (BAs). Altered metabolism serves as crucial pathogenic mechanism DKD, potentially intertwined cellular ferroptosis, lipophagy, reprogramming, immune modulation gut microbiota (thus impacting the liver-kidney axis). elucidation these mechanisms opens new potential therapeutic pathways for management. This research explores link between disruptions onset.

Language: Английский

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Oxidative stress in the brain–lung crosstalk: cellular and molecular perspectives

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: April 3, 2024

Oxidative stress is caused by an imbalance between the production of reactive oxygen species (ROS) and body’s ability to counteract their harmful effects, playing a key role in pathogenesis brain lung-related diseases. This review comprehensively examines intricate mechanisms which oxidative influences cellular molecular pathways, contributing neurodegenerative, cardiovascular, respiratory disorders. Emphasizing detrimental effects on both lung health, we discuss innovative diagnostic biomarkers, such as 8-hydroxy-2′-deoxyguanosine (8-OHdG), potential antioxidant therapies. For these topics, provide insights into future research directions field treatment, including development personalized treatment approaches, discovery validation novel new drug delivery systems. not only provides perspective understanding diseases but also offers for clinical treatments.

Language: Английский

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Advances in research on immunocyte iron metabolism, ferroptosis, and their regulatory roles in autoimmune and autoinflammatory diseases

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(7)

Published: July 4, 2024

Abstract Autoimmune diseases commonly affect various systems, but their etiology and pathogenesis remain unclear. Currently, increasing research has highlighted the role of ferroptosis in immune regulation, with cells being a crucial component body’s system. This review provides an overview discusses relationship between ferroptosis, programmed cell death cells, autoimmune diseases. Additionally, it summarizes key targets such as GPX4 TFR, responses. Furthermore, release multiple molecules, including damage-associated molecular patterns (DAMPs), following by is examined, these molecules further influence differentiation function thereby affecting occurrence progression Moreover, secrete factors or metabolites, which also impact target organs tissues involved Iron chelators, chloroquine its derivatives, antioxidants, calreticulin have been demonstrated to be effective animal studies for certain diseases, exerting anti-inflammatory immunomodulatory effects. Finally, brief summary future perspectives on are provided, aiming guide disease treatment strategies.

Language: Английский

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Tubular CD44 plays a key role in aggravating AKI through NF-κB p65-mediated mitochondrial dysfunction

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 20, 2025

Acute kidney injury (AKI) is in rapid prevalence nowadays. Of note, the underlying mechanisms have not been clarified. Several reports showed a cluster of differentiation-44 (CD44), cell-surface glycoprotein, might be involved AKI. However, its role AKI has clearly Herein, we found CD44 increased renal tubules mice. Gene ablation improved mitochondrial biogenesis and fatty acid oxidation (FAO) function, further protecting against tubular cell death injury. Conversely, ectopic impaired homeostasis exacerbated apoptosis to aggravate progression. From transcriptome sequencing, that induces mitogen-activated protein kinase (MAPK) NF-κB p65 signaling. Lipidomics also interfered with multiple aspects lipid metabolism. We deeply investigated inhibited transcription peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), resulting dysfunction apoptosis. facilitated iron intake assist ferroptosis. Hence, our study provided new mechanism for AKI, demonstrated targeted inhibition on could promising therapeutic strategy resist

Language: Английский

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Gancao Xiexin decoction attenuated experimental colitis through suppressing ACSL4-mediated ferroptosis

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119532 - 119532

Published: Feb. 1, 2025

Language: Английский

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Cholesterol-ferroptosis nexus: Unveiling novel cancer therapeutic avenues

Cancer Letters, Journal Year: 2024, Volume and Issue: 597, P. 217046 - 217046

Published: June 12, 2024

Language: Английский

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Exploring the relationship between anastasis and mitochondrial ROS-mediated ferroptosis in metastatic chemoresistant cancers: a call for investigation

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: July 2, 2024

Ferroptosis induces significant changes in mitochondrial morphology, including membrane condensation, volume reduction, cristae alteration, and outer rupture, affecting function cellular fate. Recent reports have described the intrinsic iron metabolism its intricate connection to ferroptosis, a kind of cell death characterized by dependence oxidative stress regulation. Furthermore, updated molecular insights elucidated significance mitochondria ferroptosis implications various cancers. In context cancer therapy, understanding dual role anastasis chemoresistance is crucial. Targeting pathways involved may enhance efficacy inducers, providing synergistic approach overcome chemoresistance. Research into how DNA damage response (DDR) proteins, metabolic changes, redox states interact during can offer new designing combinatorial therapeutic regimens against several cancers associated with stemness. These treatments could potentially inhibit while simultaneously inducing thereby reducing likelihood cells evading developing resistance chemotherapy. The objective this study explore interplay between anastasis, EMT chemoresistance, immunotherapeutics better understand their collective impact on therapy outcomes. We searched public research databases google scholar, PubMed, relemed, national library medicine related topic. review, we discussed tricarboxylic acid cycle glycolysis implicated modulating adding complexity regulatory mechanisms. Additionally, reactive oxygen species (ROS) electron transport chain (ETC) has garnered attention. Lipid metabolism, particularly involving GPX4 System Xc- plays both progression cancer. There need investigate clinical Integrating strategies targeting exploring potential synergy immunotherapy represent promising avenues for advancing chemoresistant treatment. Understanding among mitochondria, ROS, vital oncology, revolutionizing personalized treatment drug development.

Language: Английский

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The role of ferroptosis in neurodegenerative diseases

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Oct. 15, 2024

Ferroptosis represents an iron − and lipid peroxidation (LPO)-mediated form of regulated cell death (RCD). Recent evidence strongly suggests the involvement ferroptosis in various neurodegenerative diseases (NDs), particularly Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), multiple sclerosis (MS), amyotrophic lateral (ALS), among others. The treatment poses both opportunities challenges context ND. This review provides a comprehensive overview characteristic features, induction inhibition ferroptosis, highlighting inhibitor underlying mechanisms responsible for its occurrence. Moreover, explores how these contribute to pathogenesis progression major disorders. Additionally, it presents novel insights into role ND summarizes recent advancements development therapeutic approaches targeting ferroptosis. These hold potential guide future strategies aimed at effectively managing debilitating medical conditions.

Language: Английский

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