☆ 4.6 Review

Copper in cancer: from limiting nutrient to therapeutic target

FRONTIERS IN ONCOLOGY (2023)

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Article Chemistry, Multidisciplinary

Cuproptosis Induced by ROS Responsive Nanoparticles with Elesclomol and Copper Combined with αPD-L1 for Enhanced Cancer Immunotherapy

Boda Guo et al.

Summary: A new reactive oxygen species-sensitive polymer is designed to encapsulate elesclomol and copper, forming nanoparticles. These nanoparticles can efficiently transport copper into cancer cells and induce cell death through cuproptosis. This study combines nanomedicine-induced cuproptosis with alpha PD-L1 antibody for enhanced cancer therapy, providing a novel strategy for future cancer treatment.

ADVANCED MATERIALS (2023)

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Article Energy & Fuels

4-Octyl itaconate inhibits aerobic glycolysis by targeting GAPDH to promote cuproptosis in colorectal cancer

Wenchang Yang et al.

Summary: Cuproptosis, a new cell death pathway induced by copper, is associated with mitochondrial respiration and mediated by protein lipoylation. This study explores the role of cuproptosis in colorectal cancer progression. The results show that elesclomol-Cu inhibits cell viability and promotes apoptosis in colorectal cancer cells. Additionally, 4-Octyl itaconate (4-OI) enhances cuproptosis and inhibits aerobic glycolysis through GAPDH, leading to better anti-tumor effects in vivo.

ENERGY REPORTS (2023)

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Article Cell Biology

Prognostic and Immunological Significance of the Molecular Subtypes and Risk Signatures Based on Cuproptosis in Hepatocellular Carcinoma

Xiaolong Tang et al.

Summary: This study investigates the prognostic and immunological significance of cuproptosis in hepatocellular carcinoma (HCC) patients. The researchers identified two cuproptosis-related subtypes of HCC patients, with one subtype showing a worse prognosis and higher immune activity. They developed a prognostic risk signature based on cuproptosis-related genes, which can independently predict the prognosis of HCC patients and is associated with clinical features. Furthermore, high-risk patients were found to have a higher response rate to immune checkpoint inhibitors.

MEDIATORS OF INFLAMMATION (2023)

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Article Agriculture, Multidisciplinary

Endoplasmic Reticulum Stress Contributes to Copper-Induced Pyroptosis via Regulating the IRE1α-XBP1 Pathway in Pig Jejunal Epithelial Cells

Jianzhao Liao et al.

Summary: This study investigated the relationship between endoplasmic reticulum stress and pyroptosis in Copper-induced toxicity of the jejunum. Excess intake of Copper caused expansion of ER cavity and increased expression levels related to ER stress and pyroptosis. Inhibition of ER stress and IRE1 alpha-XBP1 pathway alleviated Copper-induced pyroptosis.

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY (2022)

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Article Gastroenterology & Hepatology

COMMD10 inhibits HIF1α/CP loop to enhance ferroptosis and radiosensitivity by disrupting Cu-Fe balance in hepatocellular carcinoma

Mi Yang et al.

Summary: The study revealed a novel role of Cu in promoting radioresistance in hepatocellular carcinoma (HCC) by disrupting Cu-Fe homeostasis through the inhibition of the HIF1 alpha/CP loop by COMMD10, enhancing ferroptosis and radiosensitivity.

JOURNAL OF HEPATOLOGY (2022)

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Review Biotechnology & Applied Microbiology

Copper-induced tumor cell death mechanisms and antitumor theragnostic applications of copper complexes

Yicheng Jiang et al.

Summary: Recent studies have shown that imbalanced copper homeostasis can affect tumor growth, causing irreversible damage. Copper can induce various forms of cell death, such as apoptosis and autophagy, through mechanisms involving reactive oxygen species accumulation, proteasome inhibition, and antiangiogenesis. This review highlights the antitumor mechanisms of copper, the development of biomaterials and nanotechnology incorporating copper, and the clinical applications of novel copper complexes.

NANOMEDICINE (2022)

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Article Biochemistry & Molecular Biology

Induction of autophagy via the ROS-dependent AMPK-mTOR pathway protects copper-induced spermatogenesis disorder

Hongrui Guo et al.

Summary: This study investigated the role of autophagy in copper-induced spermatogenesis disorder. Copper can induce autophagy via the AMPK-mTOR pathway and oxidative stress. Inhibition of autophagy increases cell damage and spermatogenesis disorder, while co-treatment with an apoptosis inhibitor can alleviate the disorder. Autophagy may also aggravate copper toxicity by promoting ferroptosis.

REDOX BIOLOGY (2022)

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Article Multidisciplinary Sciences

Copper induces cell death by targeting lipoylated TCA cycle proteins

Peter Tsvetkov et al.

Summary: Copper is an essential cofactor for all organisms, but excessive copper can lead to cell death. We found that copper-dependent cell death mechanism is different from known mechanisms, and it is related to mitochondrial respiration. Copper directly binds to lipoylated components of the tricarboxylic acid cycle, causing protein aggregation and loss of iron-sulfur cluster proteins, ultimately leading to cell death.

SCIENCE (2022)

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Review Immunology

Immunotherapy: Reshape the Tumor Immune Microenvironment

Bingzhe Lv et al.

Summary: This article reviews the function of immune cells within the tumor immune microenvironment (TIME) and discusses the contribution of current mainstream immunotherapeutic approaches to remodeling the TIME. Immunotherapy can restore the tumor killing ability of anti-tumor immune cells and shed light on better combination treatment strategies.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Oncology

Improving the Therapeutic Efficacy of Sorafenib for Hepatocellular Carcinoma by Repurposing Disulfiram

Gong Zhang et al.

Summary: The combination of DSF/Cu and sorafenib can effectively treat HCC by targeting HCSCs both in vitro and in vivo. DSF/Cu enhances the sensitivity of HCC cells to sorafenib, inhibits proliferation of HCC cells, and decreases the stemness of HCC cells.

FRONTIERS IN ONCOLOGY (2022)

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Review Oncology

Elesclomol: a copper ionophore targeting mitochondrial metabolism for cancer therapy

Peijie Zheng et al.

Summary: Elesclomol is an anticancer drug that targets mitochondrial metabolism to suppress cancer growth. It induces cell death by modulating copper levels and exhibits significant toxicity to various cancer cells. The research progress provides a possibility for the reapplication of Elesclomol and suggests combination therapy with other drugs.

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2022)

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Article Oncology

Disulfiram/Copper Induces Immunogenic Cell Death and Enhances CD47 Blockade in Hepatocellular Carcinoma

Xingxing Gao et al.

Summary: The combination of disulfiram and copper demonstrates anti-tumor effects in hepatocellular carcinoma by inducing immunogenic cell death and enhancing the efficacy of immune checkpoint blockade.

CANCERS (2022)

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Review Biochemistry & Molecular Biology

Copper homeostasis and cuproptosis in health and disease

Liyun Chen et al.

Summary: Copper is an essential micronutrient that is required for various physiological processes in almost all cell types, and its homeostasis is tightly regulated to avoid oxidative stress and cellular dysfunction. Recent studies have identified a novel form of cell death called cuproptosis, which is induced by copper binding to lipoylated enzymes in the tricarboxylic acid cycle and ultimately leads to protein aggregation, proteotoxic stress, and cell death. This article summarizes current knowledge on copper metabolism, copper-related diseases, the characteristics of cuproptosis, and the regulatory mechanisms involved. The implications of cuproptosis in the pathogenesis of diseases such as Wilson's disease, neurodegenerative diseases, and cancer are also discussed, along with the therapeutic potential of targeting cuproptosis.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2022)

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Review Nutrition & Dietetics

Copper in the tumor microenvironment and tumor metastasis

Tetsuro Kamiya

Summary: Copper dysregulation, leading to its accumulation in tumor tissues, is associated with tumor progression and metastasis. Cu transporters, Cu chaperones, and Cu-containing secretory enzymes play important roles in this process. Restricting Cu regulation may serve as a novel strategy to inhibit tumor metastasis.

JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION (2022)

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Review Oncology

Targeting ferroptosis as a vulnerability in cancer

Guang Lei et al.

Summary: This article provides an overview of the importance and potential of ferroptosis in cancer research, summarizes the mechanisms of ferroptosis induction and defense, analyzes its roles and mechanisms in tumor suppression and tumor immunity, and explores therapeutic strategies targeting ferroptosis in cancer.

NATURE REVIEWS CANCER (2022)

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Review Oncology

Connecting copper and cancer: from transition metal signalling to metalloplasia

Eva J. Ge et al.

Summary: Copper is a essential nutrient with both beneficial and toxic properties to cells. Recent progress in transition metal signaling has led to new connections between researchers from different disciplines, with potential for translating basic research into clinical therapies for diseases. The relationship between copper and cancer is particularly important, with opportunities for leveraging disease vulnerabilities through copper-dependent signaling pathways.

NATURE REVIEWS CANCER (2022)

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Review Biochemistry & Molecular Biology

Copper metabolism as a unique vulnerability in cancer

Vinit C. Shanbhag et al.

Summary: Over the past 25 years, significant progress has been made in identifying and characterizing proteins that regulate the uptake, intracellular trafficking and export of copper. While copper is essential for growth and development in humans and other mammals, it is also a limiting nutrient for cancer cell growth and proliferation. Oral copper chelators have been shown to have anti-neoplastic and anti-metastatic effects in animals and humans.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH (2021)

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Article Biotechnology & Applied Microbiology

Mitochondrial copper depletion suppresses triple-negative breast cancer in mice

Liyang Cui et al.

Summary: The research developed a mitochondria-targeted copper-depleting nanoparticle that effectively inhibited the growth of triple-negative breast cancer cells and improved survival rates in mouse models. By depriving copper within cancer cells, this approach induced metabolic changes and apoptosis, highlighting its potential clinical relevance.

NATURE BIOTECHNOLOGY (2021)

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Review Biochemistry & Molecular Biology

Mitochondrial Mechanisms of Necroptosis in Liver Diseases

Chen Xue et al.

Summary: Necroptosis is a common form of programmed cell death in the liver, activated by ligands of death receptors to form the necrosome complex. Mitochondrial-mediated necroptosis enhances oxidative respiration and generates reactive oxygen species, affecting cell susceptibility to necroptosis and interacting with mitochondrial components.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Cell Biology

Inhibiting NLRP3 inflammasome activation prevents copper-induced neuropathology in a murine model of Wilson's disease

Jianjian Dong et al.

Summary: The study demonstrates that copper-mediated neuroinflammation is associated with the activation of the NLRP3 inflammasome, contributing to progressive neuropathology in a murine model of WD. Blocking the activation of the NLRP3 inflammasome effectively mitigates cognitive decline, locomotor behavior impairment, and neurodegeneration in the mice.

CELL DEATH & DISEASE (2021)

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Article Chemistry, Medicinal

Visualization of Receptor-Interacting Protein Kinase 1 (RIPK1) by Brain Imaging with Positron Emission Tomography

Yu Lan et al.

Summary: The study developed the first PET radiotracer [F-18]CNY-07 for RIPK1/necroptosis brain imaging in rodents, which can penetrate the blood-brain barrier and showed binding specificity in animal brains. The radiotracer has the potential to be a valuable research tool for studying RIPK1-related neurological disorders in animals and potentially humans.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

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Article Multidisciplinary Sciences

Disulfiram and copper combination therapy targets NPL4, cancer stem cells and extends survival in a medulloblastoma model

Riccardo Serra et al.

Summary: This study evaluated the safety and efficacy of Disulfiram (DSF) and Copper (Cu++) in treating pediatric medulloblastoma (MB), showing significant cytotoxic effects and anti-cancer stem cell properties in vitro and in vivo experiments.

PLOS ONE (2021)

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Article Multidisciplinary Sciences

Copper depletion modulates mitochondrial oxidative phosphorylation to impair triple negative breast cancer metastasis

Divya Ramchandani et al.

Summary: Copper chelation reduces TNBC metastasis by inactivating Complex IV in sensitive SOX2/OCT4+ cells, showing potential to enrich patient populations in next-generation therapeutic trials.

NATURE COMMUNICATIONS (2021)

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Review Chemistry, Medicinal

Copper: An Intracellular Achilles' Heel Allowing the Targeting of Epigenetics, Kinase Pathways, and Cell Metabolism in Cancer Therapeutics

Filip Michniewicz et al.

Summary: Copper plays a crucial role in cancer progression by influencing cell processes, and overcoming drug resistance and relapse may require developing broader molecular targeting strategies. Overcoming these limitations may involve using copper chelating agents to simultaneously target multiple cancer treatment mechanisms.

CHEMMEDCHEM (2021)

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Article Biochemistry & Molecular Biology

Copper biology

Tiffany Tsang et al.

CURRENT BIOLOGY (2021)

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Article Biochemistry & Molecular Biology

Overcoming the compensatory elevation of NRF2 renders hepatocellular carcinoma cells more vulnerable to disulfiram/copper-induced ferroptosis

Xueying Ren et al.

Summary: DSF/Cu selectively exerts efficient cytotoxic effect on HCC cells, inhibits migration, invasion, and angiogenesis of HCC cells, impairs mitochondrial homeostasis, increases free iron pool, enhances lipid peroxidation, and eventually results in ferroptotic cell death. Inhibition of NRF2 elevation strengthens HCC cells more vulnerable to DSF/Cu induced ferroptosis.

REDOX BIOLOGY (2021)

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Article Biochemistry & Molecular Biology

Impact of Differentiated Macrophage-Like Cells on the Transcriptional Toxicity Profile of CuO Nanoparticles in Co-Cultured Lung Epithelial Cells

Matthias Hufnagel et al.

Summary: This study demonstrates that co-cultures of epithelial and immune cells can reveal additional pro-inflammatory responses of CuO nanoparticles on epithelial cells beyond the known mode of action. Using an advanced in vitro model, it extends the detection of cellular effects provoked by nanomaterials by an immunological response and emphasizes the importance of using such models to address a more comprehensive mode of action.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Engineering, Environmental

Exposure to copper induces mitochondria-mediated apoptosis by inhibiting mitophagy and the PINK1/parkin pathway in chicken ( Gallus gallus ) livers

Fan Yang et al.

Summary: The study found that Cu exposure can induce mitophagy in chicken livers through the PINK1/Parkin pathway, and that mitophagy may attenuate Cu-induced mitochondrial apoptosis.

JOURNAL OF HAZARDOUS MATERIALS (2021)

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Article Biochemistry & Molecular Biology

mtROS-mediated Akt/AMPK/mTOR pathway was involved in Copper-induced autophagy and it attenuates Copper-induced apoptosis in RAW264.7 mouse monocytes

Qin Luo et al.

Summary: Copper is a trace element necessary in animals and humans, but excessive copper can be toxic to immunocytes, leading to apoptosis and autophagy. Copper induces autophagy through the Akt/AMPK/mTOR pathway and increases autophagy through an mtROS-dependent signaling pathway. Autophagy activation potentially improves cell apoptosis induced by copper.

REDOX BIOLOGY (2021)

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Article Cell Biology

Mitochondrial regulation of ferroptosis

Boyi Gan

Summary: Mitochondria play crucial roles in driving and protecting cells in ferroptosis by actively regulating the process and providing defense mechanisms. A comprehensive understanding of mitochondrial functions holds important implications for unraveling mysteries in the field of ferroptosis.

JOURNAL OF CELL BIOLOGY (2021)

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Article Oncology

Elesclomol-induced increase of mitochondrial reactive oxygen species impairs glioblastoma stem-like cell survival and tumor growth

Mariachiara Buccarelli et al.

Summary: Elesclomol shows effective cell death induction on glioblastoma stem-like cells and GSC-derived endothelial cells, with potential as a therapeutic agent for the management of glioblastoma.

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2021)

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Article Engineering, Environmental

A tandem activation of NLRP3 inflammasome induced by copper oxide nanoparticles and dissolved copper ion in J774A.1 macrophage

Xiaoqi Tao et al.

Summary: CuONPs exposure induces inflammation in J774A.1 macrophages through NLRP3 inflammasome activation and copper ion-induced oxidative stress. CuONPs also trigger the expression of IL-1β by activating NF-κB through the TLR4 signaling pathway.

JOURNAL OF HAZARDOUS MATERIALS (2021)

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Article Oncology

Elesclomol induces copper-dependent ferroptosis in colorectal cancer cells via degradation of ATP7A

Wei Gao et al.

Summary: Elesclomol inhibits colorectal cancer by inducing copper overload, promoting oxidative stress, and regulating ferroptosis through targeting ATP7A.

MOLECULAR ONCOLOGY (2021)

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Review Biochemistry & Molecular Biology

Recent Advances in Repurposing Disulfiram and Disulfiram Derivatives as Copper-Dependent Anticancer Agents

Vinodh Kannappan et al.

Summary: Copper plays a key role in cancer progression and copper-based complexes are being investigated as novel anticancer drugs. The combination of DSF with copper has shown great anticancer potential, but DSF has proven unsuccessful in clinical trials, likely due to poor stability of the currently used oral version of DSF.

FRONTIERS IN MOLECULAR BIOSCIENCES (2021)

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Article Biochemistry & Molecular Biology

Copper metabolism in Saccharomyces cerevisiae: an update

Hua Shi et al.

Summary: Copper is an essential element in all forms of life, but excess copper ions can be harmful to cells. Saccharomyces cerevisiae is commonly used to study copper metabolism, and mechanisms such as high-affinity transporters and chaperones play a crucial role in maintaining copper homeostasis within cells.

BIOMETALS (2021)

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Article Biochemistry & Molecular Biology

Serum Copper and Zinc Levels in Patients with Endometrial Cancer

Tolga Atakul et al.

BIOLOGICAL TRACE ELEMENT RESEARCH (2020)

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Review Biochemistry & Molecular Biology

Mechanisms of Mitochondrial Iron-Sulfur Protein Biogenesis

Roland Lill et al.

ANNUAL REVIEW OF BIOCHEMISTRY, VOL 89 (2020)

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Review Cell Biology

Cell death mechanisms in eukaryotes

J. Grace Nirmala et al.

CELL BIOLOGY AND TOXICOLOGY (2020)

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Article Cell Biology

Induction of immunogenic cell death in radiation-resistant breast cancer stem cells by repurposing anti-alcoholism drug disulfiram

Ting Sun et al.

CELL COMMUNICATION AND SIGNALING (2020)

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Article Environmental Sciences

Copper sulfate-induced endoplasmic reticulum stress promotes hepatic apoptosis by activating CHOP, JNK and caspase-12 signaling pathways

Hongbin Wu et al.

ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY (2020)

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Review Biochemistry & Molecular Biology

Current Biomedical Use of Copper Chelation Therapy

Silvia Baldari et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Review Chemistry, Multidisciplinary

Old wine in new bottles: Advanced drug delivery systems for disulfiram-based cancer therapy

Anne McMahon et al.

JOURNAL OF CONTROLLED RELEASE (2020)

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Article Cell Biology

Copper Induces Oxidative Stress and Apoptosis in the Mouse Liver

Huan Liu et al.

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY (2020)

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Article Multidisciplinary Sciences

Metabolic dysregulation in the Atp7b-/- Wilson's disease mouse model

Clavia Ruth Wooton-Kee et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

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Article Oncology

Disulfiram/Copper Induces Antitumor Activity against Both Nasopharyngeal Cancer Cells and Cancer-Associated Fibroblasts through ROS/MAPK and Ferroptosis Pathways

Yiqiu Li et al.

CANCERS (2020)

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Article Cell Biology

Copper induce zebrafish retinal developmental defects via triggering stresses and apoptosis

Guang Zhao et al.

CELL COMMUNICATION AND SIGNALING (2020)

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Article Multidisciplinary Sciences

Metallothioneins regulate ATP7A trafficking and control cell viability during copper deficiency and excess

Nikita Gudekar et al.

SCIENTIFIC REPORTS (2020)

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Article Cell Biology

Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma

Tiffany Tsang et al.

NATURE CELL BIOLOGY (2020)

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Review Oncology

Understanding Metal Dynamics Between Cancer Cells and Macrophages: Competition or Synergism?

Marina Serra et al.

FRONTIERS IN ONCOLOGY (2020)

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Review Environmental Sciences

Mechanisms and pathogenesis underlying environmental chemical-induced necroptosis

Mohammad-Reza Sepand et al.

ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH (2020)

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Review Biochemistry & Molecular Biology

Copper homeostasis: Emerging target for cancer treatment

Yueqin Li

IUBMB LIFE (2020)

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Article Oncology

Intratumoral Copper Modulates PD-L1 Expression and Influences Tumor Immune Evasion

Florida Voli et al.

CANCER RESEARCH (2020)

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Article Multidisciplinary Sciences

Copper bioavailability is a KRAS-specific vulnerability in colorectal cancer

Leo Aubert et al.

NATURE COMMUNICATIONS (2020)

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Article Multidisciplinary Sciences

Serum copper, zinc and metallothionein serve as potential biomarkers for hepatocellular carcinoma

Yasuyuki Tamai et al.

PLOS ONE (2020)

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Article Oncology

Genipin enhances the antitumor effect of elesclomol in A549 lung cancer cells by blocking uncoupling protein-2 and stimulating reactive oxygen species production

Jin Hee Lee et al.

ONCOLOGY LETTERS (2020)

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Review Biochemistry & Molecular Biology

Copper Dyshomeostasis in Neurodegenerative Diseases-Therapeutic Implications

Grazyna Gromadzka et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Article Biochemistry & Molecular Biology

Serum copper and zinc levels in breast cancer: A meta-analysis

Yue Feng et al.

JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY (2020)

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Article Biochemistry & Molecular Biology

Altered copper homeostasis underlies sensitivity of hepatocellular carcinoma to copper chelation

Caroline Davis et al.

METALLOMICS (2020)

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Article Chemistry, Multidisciplinary

How trimerization of CTR1 N-terminal model peptides tunes Cu-binding and redox-chemistry

Thibaut Galler et al.

CHEMICAL COMMUNICATIONS (2020)

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Article Oncology

Inhibition of Copper Transport Induces Apoptosis in Triple-Negative Breast Cancer Cells and Suppresses Tumor Angiogenesis

Olga Karginova et al.

MOLECULAR CANCER THERAPEUTICS (2019)

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Article Biochemistry & Molecular Biology

Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer

Kirsten L. Bryant et al.

NATURE MEDICINE (2019)

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Article Multidisciplinary Sciences

ATP7A delivers copper to the lysyl oxidase family of enzymes and promotes tumorigenesis and metastasis

Vinit Shanbhag et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2019)

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Article Toxicology

Copper induces oxidative stress and apoptosis through mitochondria-mediated pathway in chicken hepatocytes

Fan Yang et al.

TOXICOLOGY IN VITRO (2019)

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Review Biochemistry & Molecular Biology

The association of serum zinc and copper with hypertension: A meta-analysis

Zhaoying Li et al.

JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY (2019)

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Review Biochemistry & Molecular Biology

The role of necroptosis in cancer biology and therapy

Yitao Gong et al.

MOLECULAR CANCER (2019)

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Review Biochemistry & Molecular Biology

Serum iron, Magnesium, Copper, and Manganese Levels in Alcoholism: A Systematic Review

Cezary Grochowski et al.

MOLECULES (2019)

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Article Biochemistry & Molecular Biology

Mitochondrial metabolism promotes adaptation to proteotoxic stress

Peter Tsvetkov et al.

NATURE CHEMICAL BIOLOGY (2019)

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Review Oncology

Repurposing Disulfiram as An Anti-Cancer Agent: Updated Review on Literature and Patents

Elmira Ekinci et al.

RECENT PATENTS ON ANTI-CANCER DRUG DISCOVERY (2019)

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Article Biotechnology & Applied Microbiology

Copper (II) Ions Activate Ligand-Independent Receptor Tyrosine Kinase (RTK) Signaling Pathway

Fang He et al.

BIOMED RESEARCH INTERNATIONAL (2019)

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Article Environmental Sciences

Inhibition of Caspase-1-dependent pyroptosis attenuates copper-induced apoptosis in chicken hepatocytes

Jianzhao Liao et al.

ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY (2019)

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Article Biochemistry & Molecular Biology

Heavy metal toxicity: An update of chelating therapeutic strategies

Jong-Joo Kim et al.

JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY (2019)

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Review Nutrition & Dietetics

Copper Deficiency: Causes, Manifestations, and Treatment

Marco Altarelli et al.

NUTRITION IN CLINICAL PRACTICE (2019)

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Article Biochemistry & Molecular Biology

The Anticancer Agent Elesclomol Has Direct Effects on Mitochondrial Bioenergetic Function in Isolated Mammalian Mitochondria

Josephine S. Modica-Napolitano et al.

BIOMOLECULES (2019)

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Article Veterinary Sciences

Hepatic copper and other trace mineral concentrations in dogs with hepatocellular carcinoma

Cailin C. Harro et al.

JOURNAL OF VETERINARY INTERNAL MEDICINE (2019)

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Article Biochemistry & Molecular Biology

The Mechanisms Underlying the Cytotoxic Effects of Copper Via Differentiated Embryonic Chondrocyte Gene 1

Ssu-Yu Chen et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2019)

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Article Gastroenterology & Hepatology

Activation of Autophagy, Observed in Liver Tissues From Patients With Wilson Disease and From ATP7B-Deficient Animals, Protects Hepatocytes From Copper-Induced Apoptosis

Elena Polishchuk et al.

GASTROENTEROLOGY (2019)

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Article Oncology

Serum copper and zinc levels at diagnosis and hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort

Ai-Ping Fang et al.

INTERNATIONAL JOURNAL OF CANCER (2019)

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Article Biochemistry & Molecular Biology

Copper affects the binding of HIF-1α to the critical motifs of its target genes

Zhijuan Wu et al.

METALLOMICS (2019)

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Article Cell Biology

Disulfiram combined with copper inhibits metastasis and epithelial-mesenchymal transition in hepatocellular carcinoma through the NF-κB and TGF-β pathways

Yi Li et al.

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE (2018)

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Review Cell Biology

Copper transporters and copper chaperones: roles in cardiovascular physiology and disease

Tohru Fukai et al.

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY (2018)

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Article Biochemistry & Molecular Biology

Association between serum copper levels and cervical cancer risk: a meta-analysis

Min Zhang et al.

BIOSCIENCE REPORTS (2018)

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Article Biochemistry & Molecular Biology

Potentiation of glutathione loss and nerve cell death by the transition metals iron and copper: Implications for age-related neurodegenerative diseases

Pamela Maher

FREE RADICAL BIOLOGY AND MEDICINE (2018)

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Article Cell Biology

DPM-1001 decreased copper levels and ameliorated deficits in a mouse model of Wilson's disease

Navasona Krishnan et al.

GENES & DEVELOPMENT (2018)

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Article Immunology

Copper Regulates the Canonical NLRP3 Inflammasome

Nikolaus Deigendesch et al.

JOURNAL OF IMMUNOLOGY (2018)

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Review Gastroenterology & Hepatology

Wilson's disease: A 2017 update

Aurelia Poujois et al.

CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY (2018)

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Article

Copper/MYC/CTR1 interplay: a dangerous relationship in hepatocellular carcinoma

Cristiana Porcu et al.

Oncotarget (2018)

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Article Biochemistry & Molecular Biology

Copper-dependent amino oxidase 3 governs selection of metabolic fuels in adipocytes

Haojun Yang et al.

PLOS BIOLOGY (2018)

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Article Medicine, Research & Experimental

Association between serum copper levels and lung cancer risk: A meta-analysis

Xiaping Zhang et al.

JOURNAL OF INTERNATIONAL MEDICAL RESEARCH (2018)

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Article Biochemistry & Molecular Biology

Copper-Binding Small Molecule Induces Oxidative Stress and Cell-Cycle Arrest in Glioblastoma-Patient-Derived Cells

Kenichi Shimada et al.

CELL CHEMICAL BIOLOGY (2018)

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Article Oncology

Influencing the Tumor Microenvironment: A Phase II Study of Copper Depletion Using Tetrathiomolybdate in Patients with Breast Cancer at High Risk for Recurrence and in Preclinical Models of Lung Metastases

Nancy Chan et al.

CLINICAL CANCER RESEARCH (2017)

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Article Multidisciplinary Sciences

Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4

Zdenek Skrott et al.

NATURE (2017)

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Review Cell Biology

Gasdermins: Effectors of Pyroptosis

Stephen B. Kovacs et al.

TRENDS IN CELL BIOLOGY (2017)

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Article Cell Biology

Disulfiram/copper selectively eradicates AML leukemia stem cells in vitro and in vivo by simultaneous induction of ROS-JNK and inhibition of NF-kB and Nrf2

Bing Xu et al.

CELL DEATH & DISEASE (2017)

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Article Multidisciplinary Sciences

Quantitative real-time imaging of glutathione

Xiqian Jiang et al.

NATURE COMMUNICATIONS (2017)

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Article Biochemistry & Molecular Biology

Mitochondrial Ferredoxin Determines Vulnerability of Cells to Copper Excess

Cindy Vallieres et al.

CELL CHEMICAL BIOLOGY (2017)

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Article Gastroenterology & Hepatology

Hepatocellular Carcinoma: An Unusual Complication of Longstanding Wilson Disease

Deepak Gunjan et al.

JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY (2017)

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Review Biochemistry & Molecular Biology

Putting p53 in Context

Edward R. Kastenhuber et al.

CELL (2017)

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Article Biochemistry & Molecular Biology

Roles of Copper in Hepatocarcinogenesis via the Activation of Hypoxia-Inducible Factor-1α

Takashi Himoto et al.

BIOLOGICAL TRACE ELEMENT RESEARCH (2016)

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Article Biophysics

How Mammalian Cells Acquire Copper: An Essential but Potentially Toxic Metal

Jack H. Kaplan et al.

BIOPHYSICAL JOURNAL (2016)

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Review Medicine, Research & Experimental

Copper dyshomoeostasis in Parkinson's disease: implications for pathogenesis and indications for novel therapeutics

Katherine M. Davies et al.

CLINICAL SCIENCE (2016)

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Letter Oncology

A phase I study of elesclomol sodium in patients with acute myeloid leukemia

David Hedley et al.

LEUKEMIA & LYMPHOMA (2016)

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Article Biochemistry & Molecular Biology

Transcriptome analysis of copper homeostasis genes reveals coordinated upregulation of SLC31A1, SCO1, and COX11 in colorectal cancer

Vincenza Barresi et al.

FEBS OPEN BIO (2016)

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Article Pharmacology & Pharmacy

Cellular mechanisms of the cytotoxicity of the anticancer drug elesclomol and its complex with Cu(II)

Brian B. Hasinoff et al.

BIOCHEMICAL PHARMACOLOGY (2015)

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Review Physiology

Behind the Link between Copper and Angiogenesis: Established Mechanisms and an Overview on the Role of Vascular Copper Transport Systems

Emanuela Urso et al.

JOURNAL OF VASCULAR RESEARCH (2015)

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Review Biochemistry & Molecular Biology

Targeting copper in cancer therapy: 'Copper That Cancer'

Delphine Denoyer et al.

METALLOMICS (2015)

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Article Chemistry, Multidisciplinary

Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation

Jing Wang et al.

NATURE CHEMISTRY (2015)

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Article Cell Biology

Copper Uptake in Mammary Epithelial Cells Activates Cyclins and Triggers Antioxidant Response

Nathalia Villa dos Santos et al.

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY (2015)

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Article Multidisciplinary Sciences

Copper depletion inhibits CoCl2-induced aggressive phenotype of MCF-7 cells via downregulation of HIF-1 and inhibition of Snail/Twist-mediated epithelial-mesenchymal transition

Shun Li et al.

SCIENTIFIC REPORTS (2015)

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Review Biotechnology & Applied Microbiology

Hypoxia-Inducible Factor-1 in Physiological and Pathophysiological Angiogenesis: Applications and Therapies

Agnieszka Zimna et al.

BIOMED RESEARCH INTERNATIONAL (2015)

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Article Toxicology

The cytotoxic mechanisms of disulfiram and copper(II) in cancer cells

Patricia Erebi Tawari et al.

TOXICOLOGY RESEARCH (2015)

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Review Biochemistry & Molecular Biology

Copper as a key regulator of cell signalling pathways

Alexandra Grubman et al.

EXPERT REVIEWS IN MOLECULAR MEDICINE (2014)

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Article Immunology

A copper chelate selectively triggers apoptosis in myeloid-derived suppressor cells in a drug-resistant tumor model and enhances antitumor immune response

Paramita Chakraborty et al.

IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY (2014)

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Article Cell Biology

Adaptive Responses of Mitochondria to Mild Copper Deprivation Involve Changes in Morphology, OXPHOS Remodeling and Bioenergetics

Lina Maria Ruiz et al.

JOURNAL OF CELLULAR PHYSIOLOGY (2014)

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Article Biochemistry & Molecular Biology

The promise of copper lowering therapy with tetrathiomolybdate in the cure of cancer and in the treatment of inflammatory disease

George J. Brewer

JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY (2014)

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Article Multidisciplinary Sciences

Copper is required for oncogenic BRAF signalling and tumorigenesis

Donita C. Brady et al.

NATURE (2014)

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Article Multidisciplinary Sciences

Upregulated Copper Transporters in Hypoxia-Induced Pulmonary Hypertension

Adriana M. Zimnicka et al.

PLOS ONE (2014)

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Review Pharmacology & Pharmacy

Existing and potential therapeutic uses for N-acetylcysteine: The need for conversion to intracellular glutathione for antioxidant benefits

Gordon F. Rushworth et al.

PHARMACOLOGY & THERAPEUTICS (2014)

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Article Biochemistry & Molecular Biology

Memo Is a Copper-Dependent Redox Protein with an Essential Role in Migration and Metastasis

Gwen MacDonald et al.

SCIENCE SIGNALING (2014)

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Article Mathematical & Computational Biology

A molecular model of human Lysyl Oxidase (LOX) with optimal copper orientation in the catalytic cavity for induced fit docking studies with potential modulators

Renganathan Bhuvanasundar et al.

BIOINFORMATION (2014)

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Article Cell Biology

Cellular glutathione plays a key role in copper uptake mediated by human copper transporter 1

Edward B. Maryon et al.

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY (2013)

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Article Oncology

Tetrathiomolybdate-associated copper depletion decreases circulating endothelial progenitor cells in women with breast cancer at high risk of relapse

S. Jain et al.

ANNALS OF ONCOLOGY (2013)

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Article Hematology

Novel Role of Copper Transport Protein Antioxidant-1 in Neointimal Formation After Vascular Injury

Takashi Kohno et al.

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY (2013)

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Article Biochemistry & Molecular Biology

Copper and Resveratrol Attenuates Serum Catalase, Glutathione Peroxidase, and Element Values in Rats with DMBA-Induced Mammary Carcinogenesis

Dorota Skrajnowska et al.

BIOLOGICAL TRACE ELEMENT RESEARCH (2013)

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Review Cell Biology

Iron and Copper in Mitochondrial Diseases

Wenjing Xu et al.

CELL METABOLISM (2013)

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Review Toxicology

The effect of zinc and the role of p53 in copper-induced cellular stress responses

Alessia Formigari et al.

JOURNAL OF APPLIED TOXICOLOGY (2013)

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Article Oncology

Final Results of Phase III SYMMETRY Study: Randomized, Double-Blind Trial of Elesclomol Plus Paclitaxel Versus Paclitaxel Alone As Treatment for Chemotherapy-Naive Patients With Advanced Melanoma

Steven J. O'Day et al.

JOURNAL OF CLINICAL ONCOLOGY (2013)

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Article Multidisciplinary Sciences

Rapid Copper Acquisition by Developing Murine Mesothelioma: Decreasing Bioavailable Copper Slows Tumor Growth, Normalizes Vessels and Promotes T Cell Infiltration

Andrew Crowe et al.

PLOS ONE (2013)

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Article Multidisciplinary Sciences

Bioavailable copper modulates oxidative phosphorylation and growth of tumors

Seiko Ishida et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2013)

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Article Oncology

Inactivation of the HIF-1α/PDK3 Signaling Axis Drives Melanoma toward Mitochondrial Oxidative Metabolism and Potentiates the Therapeutic Activity of Pro-Oxidants

Jerome Kluza et al.

CANCER RESEARCH (2012)

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Article Biochemistry & Molecular Biology

The oncology drug elesclomol selectively transports copper to the mitochondria to induce oxidative stress in cancer cells

Masazumi Nagai et al.

FREE RADICAL BIOLOGY AND MEDICINE (2012)

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Article Chemistry, Medicinal

Copper-Dependent Cytotoxicity of 8-Hydroxyquinoline Derivatives Correlates with Their Hydrophobicity and Does Not Require Caspase Activation

Saverio Tardito et al.

JOURNAL OF MEDICINAL CHEMISTRY (2012)

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Article Biochemistry & Molecular Biology

A Novel Role for Copper in Ras/Mitogen-Activated Protein Kinase Signaling

Michelle L. Turski et al.

MOLECULAR AND CELLULAR BIOLOGY (2012)

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Review Multidisciplinary Sciences

How cancer metabolism is tuned for proliferation and vulnerable to disruption

Almut Schulze et al.

NATURE (2012)

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Article Oncology

Disulfiram modulated ROS-MAPK and NFκB pathways and targeted breast cancer cells with cancer stem cell-like properties

N. C. Yip et al.

BRITISH JOURNAL OF CANCER (2011)

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Article Oncology

LOXL2-Mediated Matrix Remodeling in Metastasis and Mammary Gland Involution

Holly E. Barker et al.

CANCER RESEARCH (2011)

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Review Biochemistry & Molecular Biology

Hallmarks of Cancer: The Next Generation

Douglas Hanahan et al.

CELL (2011)

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Editorial Material Biochemistry & Molecular Biology

Copper: An essential metal in biology

Richard A. Festa et al.

CURRENT BIOLOGY (2011)

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Article Oncology

Disulfiram, and Disulfiram Derivatives as Novel Potential Anticancer Drugs Targeting the Ubiquitin Proteasome System in Both Preclinical and Clinical Studies

F. R. Kona et al.

CURRENT CANCER DRUG TARGETS (2011)

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Editorial Material Oncology

The potential for LOXL2 as a target for future cancer treatment

Holly E. Barker et al.

FUTURE ONCOLOGY (2011)

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Review Biochemistry & Molecular Biology

The significance of copper chelators in clinical and experimental application

Xueqin Ding et al.

JOURNAL OF NUTRITIONAL BIOCHEMISTRY (2011)

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Review Nutrition & Dietetics

Advances in the Understanding of Mammalian Copper Transporters

Yanfang Wang et al.

ADVANCES IN NUTRITION (2011)

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Article Marine & Freshwater Biology

Apoptosis and necroptosis are induced in rainbow trout cell lines exposed to cadmium

Gerhard Krumschnabel et al.

AQUATIC TOXICOLOGY (2010)

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Article Oncology

Enhancing Tumor-Specific Uptake of the Anticancer Drug Cisplatin with a Copper Chelator

Seiko Ishida et al.

CANCER CELL (2010)

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Article Environmental Sciences

Essentiality and Toxicity in Copper Health Risk Assessment: Overview, Update and Regulatory Considerations

Bonnie Ransom Stern

JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES (2010)

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Review Biochemistry & Molecular Biology

The missing Zinc: p53 misfolding and cancer

Stewart N. Loh

METALLOMICS (2010)

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Article Nutrition & Dietetics

Methods of assessment of copper status in humans: a systematic review

Linda J. Harvey et al.

AMERICAN JOURNAL OF CLINICAL NUTRITION (2009)

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Article Oncology

Hypoxia-Induced Lysyl Oxidase Is a Critical Mediator of Bone Marrow Cell Recruitment to Form the Premetastatic Niche

Janine T. Erler et al.

CANCER CELL (2009)

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Review Oncology

Elevated copper and oxidative stress in cancer cells as a target for cancer treatment

Anshul Gupte et al.

CANCER TREATMENT REVIEWS (2009)

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Article Oncology

Antiangiogenic Tetrathiomolybdate Protects against Her2/neu-Induced Breast Carcinoma by Hypoplastic Remodeling of the Mammary Gland

Quintin Pan et al.

CLINICAL CANCER RESEARCH (2009)

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Review Biochemistry & Molecular Biology

New Roles for Copper Metabolism in Cell Proliferation, Signaling, and Disease

Michelle L. Turski et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2009)

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Article Oncology

Phase II, Randomized, Controlled, Double-Blinded Trial of Weekly Elesclomol Plus Paclitaxel Versus Paclitaxel Alone for Stage IV Metastatic Melanoma

Steven O'Day et al.

JOURNAL OF CLINICAL ONCOLOGY (2009)

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Article Cell Biology

Mitochondrial Ubiquitin Ligase MITOL Ubiquitinates Mutant SOD1 and Attenuates Mutant SOD1-induced Reactive Oxygen Species Generation

Ryo Yonashiro et al.

MOLECULAR BIOLOGY OF THE CELL (2009)

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Review Biotechnology & Applied Microbiology

Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?

Dunyaporn Trachootham et al.

NATURE REVIEWS DRUG DISCOVERY (2009)

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Article Cell Biology

Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper

Min Ok Song et al.

PHYSIOLOGICAL GENOMICS (2009)

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Article Multidisciplinary Sciences

The iron-sulfur clusters of dehydratases are primary intracellular targets of copper toxicity

Lee Macomber et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2009)

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Article Oncology

N′1,N′3-Dimethyl-N′1,N′3-bis(phenylcarbonothioyl) Propanedihydrazide (Elesclomol) Selectively Kills Cisplatin Resistant Lung Cancer Cells through Reactive Oxygen Species (ROS)

Medhi Wangpaichitr et al.

Cancers (2009)

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Article Pharmacology & Pharmacy

Copper Regulation of Hypoxia-Inducible Factor-1 Activity

Wenke Feng et al.

MOLECULAR PHARMACOLOGY (2009)

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Article Agriculture, Dairy & Animal Science

Bioavailability of copper from copper glycinate in steers fed high dietary sulfur and molybdenum

S. L. Hansen et al.

JOURNAL OF ANIMAL SCIENCE (2008)

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Article Biochemistry & Molecular Biology

Novel role of antioxidant-1 (Atox1) as a copper-dependent transcription factor involved in cell proliferation

Shinichi Itoh et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2008)

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Article Oncology

Elesclomol induces cancer cell apoptosis through oxidative stress

Jessica R. Kirshner et al.

MOLECULAR CANCER THERAPEUTICS (2008)

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Review Biochemistry & Molecular Biology

Mechanisms for copper acquisition, distribution and regulation

Byung-Eun Kim et al.

NATURE CHEMICAL BIOLOGY (2008)

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Review Biochemistry & Molecular Biology

Menkes disease

I. Bertini et al.

CELLULAR AND MOLECULAR LIFE SCIENCES (2008)

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Review Biochemistry & Molecular Biology

Regulation of mitochondrial oxidative phosphorylation through cell signaling

Maik Huttemann et al.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH (2007)

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Article Neurosciences

Copper activates TrkB in cortical neurons in a metalloproteinase-dependent manner

Jung Jin Hwang et al.

JOURNAL OF NEUROSCIENCE RESEARCH (2007)

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Article Oncology

Reactive oxygen species: A breath of life or death?

John P. Fruehauf et al.

CLINICAL CANCER RESEARCH (2007)

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Article Oncology

Phase I clinical trial of STA-4783 in combination with paclitaxel in patients with refractory solid tumors

Anna Berkenblit et al.

CLINICAL CANCER RESEARCH (2007)

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Review Biochemistry & Molecular Biology

Supramolecular structure of the mitochondrial oxidative phosphorylation system

Egbert J. Boekema et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2007)

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Article Oncology

Disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancer cultures and xenografts via inhibition of the proteasome activity

Di Chen et al.

CANCER RESEARCH (2006)

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Article Oncology

Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by β-phenylethyl isothiocyanate

Dunyaporn Trachootham et al.

CANCER CELL (2006)

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Article Biochemistry & Molecular Biology

Gene expression signatures and biomarkers of noninvasive and invasive breast cancer cells: comprehensive profiles by representational difference analysis, microarrays and proteomics

GM Nagaraja et al.

ONCOGENE (2006)

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Article Biochemistry & Molecular Biology

A molecular role for lysyl oxidase-like 2 enzyme in Snail regulation and tumor progression

H Peinado et al.

EMBO JOURNAL (2005)

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Article Hematology

Copper-dependent activation of hypoxia-inducible factor (HIF)-1:: implications for ceruloplasmin regulation

F Martin et al.

BLOOD (2005)

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Article Pharmacology & Pharmacy

Organic copper complexes as a new class of proteasome inhibitors and apoptosis inducers in human cancer cells

KG Daniel et al.

BIOCHEMICAL PHARMACOLOGY (2004)

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Article Chemistry, Medicinal

Disulfiram facilitates intracellular Cu uptake and induces apoptosis in human melanoma cells

DZ Cen et al.

JOURNAL OF MEDICINAL CHEMISTRY (2004)

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Article Multidisciplinary Sciences

Copper chelation represses the vascular response to injury

L Mandinov et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2003)

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Article Biochemistry & Molecular Biology

Mammalian copper chaperone Cox17p has an essential role in activation of cytochrome c oxidase and embryonic development

Y Takahashi et al.

MOLECULAR AND CELLULAR BIOLOGY (2002)

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Article Cell Biology

The intracellular translocation of the components of the fibroblast growth factor 1 release complex precedes their assembly prior to export

I Prudovsky et al.

JOURNAL OF CELL BIOLOGY (2002)

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Article Biochemistry & Molecular Biology

Supercomplexes in the respiratory chains of yeast and mammalian mitochondria

H Schägger et al.

EMBO JOURNAL (2000)

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