Copper metabolism and cuproptosis in human malignancies: Unraveling the complex interplay for therapeutic insights DOI Creative Commons

K.M. Abdullah,

Jyoti Kaushal,

Simran Takkar

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(5), P. e27496 - e27496

Published: March 1, 2024

Copper, a vital trace element, orchestrates diverse cellular processes ranging from energy production to antioxidant defense and angiogenesis. Copper metabolism cuproptosis are closely linked in the context of human diseases, with particular focus on cancer. Cuproptosis refers specific type copper-mediated cell death or copper toxicity triggered by disruptions within cells. This phenomenon encompasses spectrum mechanisms, such as oxidative stress, mitochondrial dysfunction, endoplasmic reticulum perturbations metal ion equilibrium. Mechanistically, is driven binding lipoylated enzymes tricarboxylic acid (TCA) cycle. interaction participates protein aggregation proteotoxic ultimately culminating death. Targeting its associated pathways cancer cells holds therapeutic potential selectively targeting eliminating cancerous Strategies modulate levels, enhance excretion, interfere cuproptotic being explored identify novel targets for therapy improve patient outcomes. Understanding relationship between malignancies remains an active area research. review provides comprehensive overview association metabolism, homeostasis, cancers, explicitly emphasizing mechanism implications pathogenesis. Additionally, we emphasize aspects treatment.

Language: Английский

Copper metabolism in cell death and autophagy DOI Creative Commons
Qian‐Li Xue, Rui Kang, Daniel J. Klionsky

et al.

Autophagy, Journal Year: 2023, Volume and Issue: 19(8), P. 2175 - 2195

Published: April 14, 2023

Copper is an essential trace element in biological systems, maintaining the activity of enzymes and function transcription factors. However, at high concentrations, copper ions show increased toxicity by inducing regulated cell death, such as apoptosis, paraptosis, pyroptosis, ferroptosis, cuproptosis. Furthermore, can trigger macroautophagy/autophagy, a lysosome-dependent degradation pathway that plays dual role regulating survival or death fate cells under various stress conditions. Pathologically, impaired metabolism due to environmental genetic causes implicated variety human diseases, rare Wilson disease common cancers. Therapeutically, copper-based compounds are potential chemotherapeutic agents be used alone combination with other drugs approaches treat cancer. Here, we review progress made understanding metabolic processes their impact on regulation autophagy. This knowledge may help design future clinical tools improve cancer diagnosis treatment.

Language: Английский

Citations

299
Cuproptosis: A novel therapeutic target for overcoming cancer drug resistance DOI Creative Commons
Yumin Wang, Yongming Chen, Junjing Zhang

et al.

Drug Resistance Updates, Journal Year: 2023, Volume and Issue: 72, P. 101018 - 101018

Published: Nov. 11, 2023

Cuproptosis is a newly identified form of cell death driven by copper. Recently, the role copper and triggered in pathogenesis cancers have attracted attentions. has garnered enormous interest cancer research communities because its great potential for therapy. Copper-based treatment exerts an inhibiting tumor growth may open door chemotherapy-insensitive tumors. In this review, we provide critical analysis on homeostasis dysregulation development progression cancers. Then core molecular mechanisms cuproptosis discussed, followed summarizing current understanding copper-based agents (copper chelators, ionophores, complexes-based dynamic therapy) treatment. Additionally, summarize emerging data ionophores to subdue chemotherapy resistance different types We also review small-molecule compounds nanoparticles (NPs) that kill cells inducing cuproptosis, which will shed new light anticancer drugs through future. Finally, important concepts pressing questions future should be focused were discussed. This article suggests targeting could novel antitumor therapy strategy overcome drug resistance.

Language: Английский

Citations

96
A guideline on the molecular ecosystem regulating ferroptosis DOI
Enyong Dai, Xin Chen, Andreas Linkermann

et al.

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(9), P. 1447 - 1457

Published: Feb. 29, 2024

Language: Английский

Citations

74
Iron and copper: critical executioners of ferroptosis, cuproptosis and other forms of cell death DOI Creative Commons
Yu Li,

Yuhui Du,

Yujie Zhou

et al.

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Nov. 16, 2023

Abstract Regulated cell death (RCD) is a regulable that involves well-organized signaling cascades and molecular mechanisms. RCD implicated in fundamental processes such as organ production tissue remodeling, removing superfluous structures or cells, regulating numbers. Previous studies have not been able to reveal the complete mechanisms, novel methods of are constantly being proposed. Two metal ions, iron (Fe) copper (Cu) essential factors leading RCDs only induce ferroptosis cuproptosis, respectively but also lead impairment eventually diverse death. This review summarizes direct indirect mechanisms by which Fe Cu impede growth various forms mediated these two metals. Moreover, we aimed delineate interrelationships between with distinct pathways shedding light on complex intricate govern cellular survival Finally, prospects outlined this suggest approach for investigating death, may involve integrating current therapeutic strategies offer promising solution overcome drug resistance certain diseases.

Language: Английский

Citations

72
Oxidative cell death in cancer: mechanisms and therapeutic opportunities DOI Creative Commons
Xiaoqin An, Wenfeng Yu, Jinbao Liu

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(8)

Published: Aug. 1, 2024

Abstract Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules generated as natural byproducts during cellular processes, including metabolism. Under normal conditions, ROS play crucial roles in diverse functions, cell signaling and immune responses. However, a disturbance the balance between production antioxidant defenses can lead to an excessive buildup, causing oxidative stress. This stress damages essential components, lipids, proteins, DNA, potentially culminating death. form of death take various forms, such ferroptosis, apoptosis, necroptosis, pyroptosis, paraptosis, parthanatos, oxeiptosis, each displaying distinct genetic, biochemical, characteristics. The investigation holds promise for development pharmacological agents that used prevent tumorigenesis or treat established cancer. Specifically, targeting key SLC7A11, GCLC, GPX4, TXN, TXNRD, represents emerging approach inducing cancer cells. review provides comprehensive summary recent progress, opportunities, challenges therapy.

Language: Английский

Citations

64
The mechanism of ferroptosis and its related diseases DOI Creative Commons
Shijian Feng, Dan Tang, Yichang Wang

et al.

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Oct. 16, 2023

Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation lipid peroxides, provides novel avenue for delving into intersection metabolism, oxidative stress, and disease pathology. We have witnessed mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, traumatic tissue injuries. By unraveling intricate underpinnings molecular machinery, contributors, signaling conduits, regulatory networks governing researchers aim bridge gap between intricacies this unique mode multifaceted implications health disease. In light rapidly advancing landscape ferroptosis research, we present comprehensive review aiming at extensive in origins progress human diseases. This concludes careful analysis potential treatment approaches carefully designed either inhibit or promote ferroptosis. Additionally, succinctly summarized therapeutic targets compounds that hold promise targeting within various facet underscores burgeoning possibilities manipulating as strategy. summary, enriched insights both investigators practitioners, while fostering an elevated comprehension latent translational utilities. revealing basic processes investigating possibilities, crucial resource scientists medical aiding deep understanding effects situations.

Language: Английский

Citations

62
International consensus guidelines for the definition, detection, and interpretation of autophagy-dependent ferroptosis DOI Creative Commons
Xin Chen,

Andrey S. Tsvetkov,

Han‐Ming Shen

et al.

Autophagy, Journal Year: 2024, Volume and Issue: 20(6), P. 1213 - 1246

Published: March 6, 2024

Macroautophagy/autophagy is a complex degradation process with dual role in cell death that influenced by the types are involved and stressors they exposed to. Ferroptosis an iron-dependent oxidative form of characterized unrestricted lipid peroxidation context heterogeneous plastic mechanisms. Recent studies have shed light on involvement specific autophagy (e.g. ferritinophagy, lipophagy, clockophagy) initiating or executing ferroptotic through selective anti-injury proteins organelles. Conversely, other forms reticulophagy lysophagy) enhance cellular defense against damage. Dysregulated autophagy-dependent ferroptosis has implications for diverse range pathological conditions. This review aims to present updated definition ferroptosis, discuss influential substrates receptors, outline experimental methods, propose guidelines interpreting results.

Language: Английский

Citations

58
Targeting GPX4 in human cancer: Implications of ferroptosis induction for tackling cancer resilience DOI
Jaewang Lee, Jong‐Lyel Roh

Cancer Letters, Journal Year: 2023, Volume and Issue: 559, P. 216119 - 216119

Published: March 7, 2023

Language: Английский

Citations

57
Copper homeostasis and cuproptosis in cancer immunity and therapy DOI Open Access

Wei‐Qing Liu,

Wanrong Lin, Yan Li

et al.

Immunological Reviews, Journal Year: 2023, Volume and Issue: 321(1), P. 211 - 227

Published: Sept. 16, 2023

Summary Copper is an essential nutrient for maintaining enzyme activity and transcription factor function. Excess copper results in the aggregation of lipoylated dihydrolipoamide S‐acetyltransferase (DLAT), which correlates to mitochondrial tricarboxylic acid (TCA) cycle, resulting proteotoxic stress eliciting a novel cell death modality: cuproptosis. Cuproptosis exerts indispensable role cancer progression, considered promising strategy therapy. Cancer immunotherapy has gained extensive attention owing breakthroughs immune checkpoint blockade; furthermore, cuproptosis strongly connected modulation antitumor immunity. Thus, thorough recognition concerning mechanisms involved metabolism may facilitate improvement management. This review outlines cellular molecular characteristics links regulated modality with human cancers. We also current knowledge on complex effects immunity response. Furthermore, potential agents that elicit pathways are summarized. Lastly, we discuss influence induction tumor microenvironment as well challenges adding regulators therapeutic strategies beyond traditional

Language: Английский

Citations

52
Ferroptosis: principles and significance in health and disease DOI Creative Commons
Fangquan Chen, Rui Kang, Daolin Tang

et al.

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

Citations

51