Stigmasterol and barasertib target cuproptosis-related prognostic model for the synergistic treatment of breast cancer. DOI Creative Commons

Yongqin wang wang,

Yuxiao Ma,

Junyi Tan

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 14, 2023

Abstract Background Breast cancer (BRCA) has a high incidence and poor prognosis. Cuproptosis is crucial regulator of carcinogenesis tumor progression. However, it not been reported how cuproptosis in BRCA patients treated using Chinese Western medicines. Methods This study investigated used to diagnose treat BRCA. A prognostic model was constructed bioinformatics approach. We LASSO establish associated with cuproptosis, demonstrated the reliability survival analysis. Results CIBERSORT analysis showed that immune infiltration. An interesting finding from CellMiner database revealed correlation between risk score Barasertib. According network pharmacology molecular docking analysis, stigmasterol, an active ingredient Curcuma longa L., may target gene ADAM9 model. The combination drugs confirmed stigmasterol barasertib had significant synergistic effect on cells. Conclusion Our provides potential strategy for treating medicines

Language: Английский

Ferroptosis inducers enhanced cuproptosis induced by copper ionophores in primary liver cancer DOI Creative Commons

Wei‐Kai Wang,

Kaizhong Lu, Xin Jiang

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: June 6, 2023

Cuproptosis and ferroptosis are the two newly defined metal-related regulated cell death. However, crosstalk between cuproptosis is obscure.We analyzed effect of inducers on copper ionophores-induced death through CCK-8 assay. was studied using immunofluorescence protein soluble-insoluble fraction isolation. GSH assay, qRT-PCR western blot were adopted to explore machinery enhanced cuproptosis. And mouse xenograft model built detect synergy elesclomol-Cu sorafenib in vivo.Herein we found that erastin could enhance primary liver cancer cells by increasing dependent lipoylated aggregation. Mechanically, upregulated lipoylation via suppressing mitochondrial matrix-related proteases mediated ferredoxin 1 (FDX1) degradation, reduced intracellular chelator glutathione (GSH) synthesis inhibiting cystine importing.Our findings proposed combination ionophores co-targeting be a novel therapeutic strategy for cancer.

Language: Английский

Citations

124
Current Trends on the Involvement of Zinc, Copper, and Selenium in the Process of Hepatocarcinogenesis DOI Open Access
Takashi Himoto, Tsutomu Masaki

Nutrients, Journal Year: 2024, Volume and Issue: 16(4), P. 472 - 472

Published: Feb. 6, 2024

Numerous nutritional factors increase the risk of hepatocellular carcinoma (HCC) development. The dysregulation zinc, copper, and selenium homeostasis is associated with occurrence HCC. impairment these essential trace elements results in oxidative stress, DNA damage, cell cycle progression, angiogenesis, finally leading to hepatocarcinogenesis. These can affect microenvironment carrier proteins for zinc copper selenium-containing enzymes play important roles prevention or progression enhance alleviate chemosensitivity anticancer agents patients may other each other. Novel types death including ferropotosis cupropotosis are also Therapeutic strategies HCC that target have been developed vitro vivo studies. use zinc-, copper- selenium-nanoparticles has considered as novel therapeutic indicate become promising targets clinical application an urgent unmet requirement. This review article highlights correlation between development summarizes current trends on pathogenesis

Language: Английский

Citations

14
Taxifolin regulates SLC31A1-mediated cuproptosis and tumor progression in hepatocellular carcinoma DOI
Jike Li,

Yuelian Wang,

Lei Bao

et al.

Human Cell, Journal Year: 2025, Volume and Issue: 38(2)

Published: Jan. 3, 2025

Language: Английский

Citations

1
Copper in hepatocellular carcinoma： A double-edged sword with therapeutic potentials DOI

Zixin Wu,

Guishuai Lv,

Fuxue Xing

et al.

Cancer Letters, Journal Year: 2023, Volume and Issue: 571, P. 216348 - 216348

Published: Aug. 9, 2023

Language: Английский

Citations

22
Novel insights into anticancer mechanisms of elesclomol: More than a prooxidant drug DOI Creative Commons

Jialing Gao,

Xiaoxue Wu, Shuting Huang

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 67, P. 102891 - 102891

Published: Sept. 17, 2023

As an essential micronutrient for humans, the metabolism of copper is fine-tuned by evolutionarily conserved homeostatic mechanisms. Copper toxicity occurs when its concentration exceeds a certain threshold, which has been exploited in development ionophores, such as elesclomol, anticancer treatment. Elesclomol garnered recognition potent drug and evaluated numerous clinical trials. However, mechanisms underlying elesclomol-induced cell death remain obscure. The discovery cuproptosis, novel form triggered targeted accumulation mitochondria, redefines significance elesclomol cancer therapy. Here, we provide overview homeostasis associated pathological disorders, especially carcinogenesis. We summarize our current knowledge tumor suppressive with emphasis on cuproptosis. Finally, discuss strategies that may contribute to better application

Language: Английский

Citations

17
Copper homeostasis and cuproptosis in health and disease DOI Creative Commons

Yunuo Yang,

Jiaxuan Wu,

Lisheng Wang

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(10)

Published: Sept. 17, 2024

Copper is a vital trace element in human physiology, essential for the synthesis of numerous crucial metabolic enzymes and facilitation various biological processes. Regulation copper levels within narrow range imperative maintaining homeostasis. Numerous studies have demonstrated significant roles homeostasis cuproptosis health disease pathogenesis. However, comprehensive up-to-date systematic review this domain remains absent. This aims to consolidate recent advancements understanding disease, focusing on underlying mechanisms potential therapeutic interventions. Dysregulation homeostasis, manifesting as either excess or deficiency, implicated etiology diseases. Cuproptosis, recently identified form cell death, characterized by intracellular overload. phenomenon mediates diverse array evolutionary processes organisms, spanning from genetic disorders, liver diseases, neurodegenerative cancers. provides summary pathogenic along with associated targeted agents. Furthermore, it explores future research directions yield treatment, management, prevention.

Language: Английский

Citations

7
Intestinal Cu(II)/(I) Redox State Transformation Causes Cu(I) Overflow and Toxicity of the Gut and Liver in Zebrafish DOI
Wanying Gui, Wen‐Xiong Wang

Environmental Science & Technology, Journal Year: 2025, Volume and Issue: unknown

Published: April 13, 2025

Copper (Cu) has long been a concern for human health. While previous studies have explored the toxic effects of Cu, no study is available on relationship between Cu redox state transformation and biotoxicity in higher organisms. In this study, we gut liver toxicity caused by overflow Cu(I) at low doses exposure. Here, first elucidated digestive metabolic systems as main target sites systematic epidemiological analysis. Then, ICP-MS analysis verified that were top two Cu-high-accumulated organs zebrafish exposed to 10 100 μg/L waterborne 72 h. In-situ Cu(II) imaging techniques demonstrated exogenous was converted gut. Furthermore, transcriptomic sequencing revealed high induced cell cycle arrest G phase. However, substantial accumulation disrupted metabolism energy source nutrients supply, leading hepatic toxicity. This provides new insights into mechanism based emphasizes health risks associated with exposure systems.

Language: Английский

Citations

0
FN1 Immunoregulation in Glioblastoma: Insights From Neutrophil‐Centric Studies DOI Creative Commons
Xiangtian Meng, Xiaoming Yang,

Junle Zhu

et al.

Cancer Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Neutrophils, as key components of the tumor microenvironment, play a crucial role in cancer progression and prognosis. This study aimed to identify neutrophil-related gene signature improve prognostic predictions explore potential immunotherapy targets for glioblastoma multiforme (GBM) patients. Through co-expression analysis, 60 neutrophil-associated genes were identified, showing significant enrichment 159 Gene Ontology terms eight KEGG pathways. Among these, 10 significantly associated with patient survival, leading development six-gene risk model termed Neutrophil-Related Prognostic Index (NRGPI). The NRGPI predicted overall survival (OS) both training validation cohorts (p < 0.05), enhanced accuracy when combined clinicopathological factors. Higher scores correlated worse OS, increased mortality, more aggressive disease progression. Immune profiling linked immune cell infiltration, checkpoint expression, mutation burden, suggesting its identifying candidates immunotherapy. identified genes, FN1 emerged central regulator, composition poor Pan-cancer analysis revealed consistent upregulation across types, underscoring broad clinical relevance. Additionally, tissue microarray using multiplex immunofluorescence on 84 GBM samples confirmed FN1, SDC1, TWIST1, higher levels reduced survival. These findings establish valuable biomarker GBM, offering novel insights into landscape positioning promising therapeutic target further investigation treatment.

Language: Английский

Citations

0
Cuproptosis-related genes and agents: implications in tumor drug resistance and future perspectives DOI Creative Commons

Lingwen Xu,

Xiaolan Cao,

Yuxiao Deng

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: May 8, 2025

In the field of tumor treatment, drug resistance remains a significant challenge requiring urgent intervention. Recent developments in cell death research have highlighted cuproptosis, mechanism induced by copper, as promising avenue for understanding biology and addressing resistance. Cuproptosis is initiated dysregulation copper homeostasis, which turn triggers mitochondrial metabolic disruptions induces proteotoxic stress. This process specifically entails accumulation lipoylated proteins depletion iron-sulfur cluster within context tricarboxylic acid cycle. Simultaneously, it accompanied activation distinct signaling pathways that collectively lead to death. Emerging evidence highlights critical role cuproptosis However, core molecular mechanisms regulation microenvironment, clinical translation still require further exploration. review examines intersection resistance, detailing essential roles cuproptosis-related genes exploring therapeutic potential ionophores, chelators, nanodelivery systems. These offer promise overcoming advancing precision medicine. By elucidating underlying this study aims identify novel strategies targets, thereby paving way development innovative anti-cancer drugs.

Language: Английский

Citations

0
Copper homeostasis and copper-induced cell death in tumor immunity: implications for therapeutic strategies in cancer immunotherapy DOI Creative Commons

Sai‐Nan Zhang,

Qibo Huang,

Tuo Ji

et al.

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Oct. 31, 2024

Copper is an important trace element for maintaining key biological functions such as cellular respiration, nerve conduction, and antioxidant defense. Maintaining copper homeostasis critical human health, its imbalance has been linked to various diseases, especially cancer. Cuproptosis, a novel mechanism of copper-induced cell death, provides new therapeutic opportunities metal ion regulation interact with fate. This review insights into the complex mechanisms metabolism, molecular basis cuproptosis, association cancer development. We assess role cuproptosis-related genes (CRGs) associated tumorigenesis, their importance prognostic indicators targets, impact on tumor microenvironment (TME) immune response. Ultimately, this highlights interplay between copper, immunotherapy.

Language: Английский

Citations

2