Cuproptosis: mechanisms and links with cancers

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: March 7, 2023

Abstract Cuproptosis was a copper-dependent and unique kind of cell death that separate from existing other forms death. The last decade has witnessed considerable increase in investigations programmed death, whether copper induced an independent form long been argued until mechanism cuproptosis revealed. After that, increasing number researchers attempted to identify the relationship between process cancer. Thus, this review, we systematically detailed systemic cellular metabolic processes copper-related tumor signaling pathways. Moreover, not only focus on discovery its mechanism, but also outline association cancers. Finally, further highlight possible therapeutic direction employing ion ionophores with cuproptosis-inducing functions combination small molecule drugs for targeted therapy treat specific

Language: Английский

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Cuproptosis-Related Risk Score Predicts Prognosis and Characterizes the Tumor Microenvironment in Hepatocellular Carcinoma

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: July 11, 2022

Aims Cuproptosis is a recently identified form of programmed cell death; however, its role in hepatocellular carcinoma (HCC) remains unclear. Methods A set bioinformatic tools was integrated to analyze the expression and prognostic significance ferredoxin 1 ( FDX1 ), key regulator cuproptosis. cuproptosis-related risk score (CRRS) developed via correlation analyses, least absolute shrinkage selection operator (LASSO) Cox regression, multivariate regression. The metabolic features, mutation signatures, immune profile CRRS-classified HCC patients were investigated, CRRS therapy guidance analyzed. Results significantly downregulated HCC, high associated with longer survival time. high-CRRS group showed lower overall (OS) enriched cancer-related pathways. Mutation analyses revealed that had mutational frequency some tumor suppressors such as protein P53 TP53 ) Breast-cancer susceptibility gene (BRCA1)-associated BAP1 low catenin beta CTNNB1 ). Besides, an increase protumor infiltrates checkpoints. Moreover, area under curve (AUC) values predicting efficiency sorafenib non-responsiveness transcatheter arterial chemoembolization (TACE) reached 0.877 0.764, respectively. Significance signature helpful prediction guiding treatment for patients.

Language: Английский

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A Hollow Amorphous Bimetal Organic Framework for Synergistic Cuproptosis/Ferroptosis/Apoptosis Anticancer Therapy via Disrupting Intracellular Redox Homeostasis and Copper/Iron Metabolisms

Advanced Functional Materials, Journal Year: 2022, Volume and Issue: 32(40)

Published: July 30, 2022

Abstract Cuproptosis is a very newly recognized regulated cell death modality that distinct from known mechanisms and shows enormous prospect in cancer treatment. However, its efficacy copper‐dependent restricted by strictly copper metabolism. Herein, novel copper/iron hybrid hollow amorphous metal organic framework (HaMOF) developed as an oxidative stress amplifier metabolic disrupter for synergistic cuproptosis/ferroptosis/apoptosis anticancer therapy. The HaMOF fabricated Cu 2+ , 3,3′‐dithiobis(propionohydrazide) Fe 3+ via unsaturated coordination‐etching integration strategy, then doxorubicin loaded followed surface decoration with hyaluronan. obtained DOX@Fe/CuTH exhibits tumor microenvironment‐triggered catalytic therapeutic property, wherein it can amplify cellular simultaneously boosting H 2 O production depleting glutathione. Moreover, cause mitochondrial dysfunction downregulate the expressions of transporter ATP7A iron FPN 1, thereby leading to disorders high retentions cytoplasm •OH generation. overloaded lipoylated protein dihydrolipoamide S‐acetyltransferase aggregation lead cuproptosis. Collectively, both augmented induce potent ferroptosis, which synergizes cuproptosis DOX‐mediated apoptosis efficiently suppress growth. This bimetallic nanoplatform provides new paradigm boost cuproptosis‐related therapies.

Language: Английский

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Copper homeostasis and copper-induced cell death in the pathogenesis of cardiovascular disease and therapeutic strategies

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(2)

Published: Feb. 11, 2023

Abstract Copper is a vital mineral, and an optimal amount of copper required to support normal physiologic processes in various systems, including the cardiovascular system. Over past few decades, copper-induced cell death, named cuproptosis, has become increasingly recognized as important process mediating pathogenesis progression disease (CVD), atherosclerosis, stroke, ischemia-reperfusion injury, heart failure. Therefore, in-depth understanding regulatory mechanisms cuproptosis CVD may be useful for improving management. Here, we review relationship between homeostasis cuproptosis-related pathways CVD, well therapeutic strategies addressing death CVD.

Language: Английский

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Photothermally Triggered Copper Payload Release for Cuproptosis‐Promoted Cancer Synergistic Therapy

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(12)

Published: Dec. 31, 2022

Abstract Cuproptosis is a new form of programmed cell death and exhibits enormous potential in cancer treatment. However, reducing the undesirable Cu ion release normal tissue maximizing copper‐induced therapeutic effect sites are two main challenges. In this study, we constructed photothermally triggered nanoplatform (Au@MSN‐Cu/PEG/DSF) to realize on‐demand delivery for synergistic therapy. The released disulfiram (DSF) chelated with 2+ situ generate highly cytotoxic bis(diethyldithiocarbamate)copper (CuET), causing apoptosis, formed + species promoted toxic mitochondrial protein aggregation, leading cuproptosis. Synergistic photothermal therapy, Au@MSN‐Cu/PEG/DSF could effectively kill tumor cells inhibit growth (inhibition rate up 80.1 %). These results provide promising perspective treatment based on cuproptosis, may also inspire design advanced nano‐therapeutic platforms.

Language: Английский

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Cuproptosis: A novel therapeutic target for overcoming cancer drug resistance

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

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Copper in cancer: From pathogenesis to therapy

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 163, P. 114791 - 114791

Published: April 25, 2023

One of the basic trace elements for structure and metabolism human tissue is copper. However, as a heavy metal, excessive intake or abnormal accumulation copper in body can cause inevitable damage to organism because result direct injury various cell components disruption redox balance, eventually leading death. Interestingly, growing research reports that diverse cancers have raised serum tumor levels. Tumor cells depend on more their than normal cells, decrease overload detrimental effect cells. New modalities identifying characterizing copper-dependent signals offer translational opportunities therapy, but mechanisms remain unclear. Therefore, this article summarizes what we currently know about correlation between cancer describes characteristics prospective application copper-derived therapeutics.

Language: Английский

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Tumor Microenvironment Responsive Hollow Nanoplatform for Triple Amplification of Oxidative Stress to Enhance Cuproptosis‐Based Synergistic Cancer Therapy

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(13)

Published: Jan. 30, 2023

Cuproptosis is a recently discovered form of programmed cell death and shows great potential in cancer treatment. Herein, copper-dithiocarbamate chelate-doped artemisinin-loaded hollow nanoplatform (HNP) developed via chelation competition-induced hollowing strategy for cuproptosis-based combination therapy. The HNP exhibits tumor microenvironment-triggered catalytic activity, wherein liberated Cu2+ catalyzes artemisinin endogenous H2 O2 to produce C-centered radicals hydroxyl radicals, respectively. Meanwhile, the disulfide bonds-rich can deplete intracellular glutathione, thus triply amplifying oxidative stress. augmented stress sensitizes cells cuproptosis, causing prominent dihydrolipoamide S-acetyltransferase oligomerization mitochondrial dysfunction. Moreover, activate ferroptosis inhibiting GPX4 activity trigger apoptosis dithiocarbamate-copper chelate-mediated ubiquitinated proteins accumulation, resulting potent antitumor efficacy. Such cuproptosis/ferroptosis/apoptosis synergetic opens new avenue

Language: Английский

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H₂S‐Activated Ion‐Interference Therapy: A Novel Tumor Targeted Therapy Based on Copper‐Overload‐Mediated Cuproptosis and Pyroptosis

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 33(38)

Published: June 6, 2023

Abstract Copper overload is a novel way to achieve copper‐ion‐interference therapy by disrupting copper homeostasis and treating diseases through multiple cell death pathways. However, it difficult reach since excess intracellular ions will be pumped out. Herein, achieved both raising cellular uptake reducing the efflux of using hydrogen sulfide (H 2 S)‐responsive hydroxyphosphate nanoparticles (Cu (PO 4 )(OH) NPs). After immersion in an H S‐enriched colon cancer microenvironment, Cu NPs can transform into with reduced size for higher entering, resulting improved Fenton activity as well ion dissociation. Reactive oxygen species generated reaction not only activate inflammasomes Caspase‐1 proteins, cause cleavage gasdermin D induce pyroptosis, but also affect mitochondrial function down‐regulate exporter ATP7A further reduce excretion. The combination endocytosis lower exportation leads maximized overload. Together efficient release, tricarboxylic acid cycle disrupted iron‐sulfur cluster proteins are downregulated, ultimately triggering cuproptosis. As pyroptosis cuproptosis ways death, this study provides realize effective tumor‐targeted based on S‐activated simple NPs.

Language: Английский

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The copper age in cancer treatment: From copper metabolism to cuproptosis

Progress in Materials Science, Journal Year: 2023, Volume and Issue: 138, P. 101145 - 101145

Published: May 23, 2023

Language: Английский

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