The crosstalk between copper-induced oxidative stress and cuproptosis: a novel potential anticancer paradigm

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Июль 5, 2024

Abstract Copper is a crucial trace element that plays role in various pathophysiological processes the human body. also acts as transition metal involved redox reactions, contributing to generation of reactive oxygen species (ROS). Under prolonged and increased ROS levels, oxidative stress occurs, which has been implicated different types regulated cell death. The recent discovery cuproptosis, copper-dependent death pathway distinct from other known forms, raised interest researchers field cancer therapy. Herein, present work aims outline current understanding with an emphasis on its anticancer activities through interplay copper-induced stress, thereby providing new ideas for therapeutic approaches targeting modes future.

Язык: Английский

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Unveiling the promising anticancer effect of copper-based compounds: a comprehensive review

Journal of Cancer Research and Clinical Oncology, Год журнала: 2024, Номер 150(4)

Опубликована: Апрель 25, 2024

Abstract Copper is a necessary micronutrient for maintaining the well-being of human body. The biological activity organic ligands, especially their anticancer activity, often enhanced when they coordinate with copper(I) and (II) ions. its compounds are capable inducing tumor cell death through various mechanisms action, including activation apoptosis signaling pathways by reactive oxygen species (ROS), inhibition angiogenesis, induction cuproptosis, paraptosis. Some copper complexes currently being evaluated in clinical trials ability to map hypoxia cancers, locally advanced rectal cancer bulky tumors. Several studies have shown that nanoparticles can be used as effective agents chemodynamic therapy, phototherapy, hyperthermia, immunotherapy. Despite promising copper-based compounds, use subject certain limitations. Elevated concentrations may promote growth, metastasis affecting cellular processes.

Язык: Английский

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

Cancers, Год журнала: 2024, Номер 16(3), С. 512 - 512

Опубликована: Янв. 24, 2024

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

Язык: Английский

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Cuproptosis: Unraveling the Mechanisms of Copper-Induced Cell Death and Its Implication in Cancer Therapy

Cancers, Год журнала: 2024, Номер 16(3), С. 647 - 647

Опубликована: Фев. 2, 2024

Copper, an essential element for various biological processes, demands precise regulation to avert detrimental health effects and potential cell toxicity. This paper explores the mechanisms of copper-induced death, known as cuproptosis, its disease implications, including cancer therapy. Copper ionophores, such elesclomol disulfiram, increase intracellular copper levels. elevation triggers oxidative stress subsequent offering implications in Additionally, ionophores disrupt mitochondrial respiration protein lipoylation, further contributing toxicity death. Potential targets biomarkers are identified, can be targeted those proteins trigger cuproptosis. The role different cancers is discussed understand therapies using nanomaterials, chelators. Furthermore, explored through diseases Wilson Menkes physiological copper. Exploring cuproptosis presents opportunity improve treatments copper-related disorders cancers, with bring significant advancements modern medicine.

Язык: Английский

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Current Trends on the Involvement of Zinc, Copper, and Selenium in the Process of Hepatocarcinogenesis

Nutrients, Год журнала: 2024, Номер 16(4), С. 472 - 472

Опубликована: Фев. 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

Язык: Английский

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Cuproptosis and Cu: a new paradigm in cellular death and their role in non-cancerous diseases

APOPTOSIS, Год журнала: 2024, Номер 29(9-10), С. 1330 - 1360

Опубликована: Июль 16, 2024

Язык: Английский

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Ferroptosis and cuproptosis: Metal-dependent cell death pathways activated in response to classical chemotherapy – Significance for cancer treatment?

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2024, Номер 1879(4), С. 189124 - 189124

Опубликована: Май 25, 2024

Apoptosis has traditionally been regarded as the desired cell death pathway activated by chemotherapeutic drugs due to its controlled and non-inflammatory nature. However, recent discoveries of alternative pathways have paved way for immune-stimulatory treatment approaches in cancer. Ferroptosis (dependent on iron) cuproptosis copper) hold promise selective cancer targeting overcoming drug resistance. Copper ionophores iron-bearing nano-drugs show potential clinical therapy single agents adjuvant treatments. Here we review up-to-date evidence involvement metal ion-dependent cytotoxicity classical (alkylating agents, topoisomerase inhibitors, antimetabolites, mitotic spindle inhibitors) their combinations with ferroptosis inducers, indicating prospects, advantages, obstacles use.

Язык: Английский

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AKT1 Phosphorylates FDX1 to Promote Cuproptosis Resistance in Triple‐Negative Breast Cancer

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Фев. 20, 2025

Abstract Cuproptosis, a recently defined copper‐dependent cell death pathway, remains largely unexplored in tumor therapies, particularly breast cancer. This study demonstrates that triple‐negative cancer (TNBC) bears relatively elevated copper levels and exhibits resistance to cuproptosis. Mechanistically, activates the AKT signaling which inhibits ferredoxin‐1 (FDX1), key regulator of AKT1‐mediated FDX1 phosphorylation not only abrogates FDX1‐induced cuproptosis aerobic respiration but also promotes glycolysis. Consequently, combination AKT1 inhibitors ionophores synergistically alleviate TNBC tumorigenesis both vitro vivo. In summary, findings reveal crucial mechanism underlying suggest potential therapeutic approach for TNBC.

Язык: Английский

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The Importance of Being Casiopeina as Polypharmacologycal Profile (Mixed Chelate–Copper (II) Complexes and Their In Vitro and In Vivo Activities)

Inorganics, Год журнала: 2023, Номер 11(10), С. 394 - 394

Опубликована: Окт. 7, 2023

In this review, we present a timeline that shows the origin of mixed chelate copper (II) complexes, registered as Mark Title Casiopeínas®, first compounds proposed anticancer drugs in 1988 and 1992. late twentieth century, use essential metals agents was not even considered, except for their antifungal or antibacterial effects; also, copper, gold salts, used arthritis problems. The to diminish secondary toxic effects Cisplatin our driving force: find less more economical under rational design metal complexes. Due chemical properties, were choice continue drug development. order ideas, designs chelate–copper complexes (Casiopeínas, (Cas) homoleptic heteroleptic, depending on nature ligand) synthesized fully characterized. search new, effective, drugs, Casiopeína® emerged family approximately 100 from coordinated Cu(II) with proven antineoplastic potential through cytotoxic action. Cas have general formula [Cu(N–N)(N–O)]NO3 [Cu(N–N)(O–O)]NO3, where N–N is an aromatic substituted diimine (1,10-phenanthroline 2,2′-bipyridine), oxygen donor (O–O) acetylacetonate salicylaldehyde. Lately, some similar been developed by other research groups considering hypothesis after Casiopeína’s discoveries had published, described herein. As example translational medicine criteria, covered each step established normative process development, consequently, one molecules (Casiopeína III ia (CasIIIia)) has reached clinical phase I. For these compounds, activities, such antibacterial, antiparasitic antiviral, discovered.

Язык: Английский

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Is Copper Still Safe for Us? What Do We Know and What Are the Latest Literature Statements?

Current Issues in Molecular Biology, Год журнала: 2024, Номер 46(8), С. 8441 - 8463

Опубликована: Авг. 2, 2024

Copper (Cu) is a precious metal and one of the three most abundant trace elements in body (50-120 mg). It involved large number cellular mechanisms pathways an essential cofactor function enzymes. Both its excess deficiency may be harmful for many diseases. Even small changes Cu concentration associated with significant toxicity. Consequently, it can damaging to any organ or tissue our body, beginning effects already at molecular level then affecting degradation individual tissues/organs slow development diseases, such as those immunological system, skeletal circulatory nervous digestive respiratory reproductive skin. The main purpose this article review literature regard both healthiness toxicity copper human body. A secondary objective show widespread use sources, including food common materials contact humans. Its biological half-life from diet estimated range 13 33 days. retention bioavailability influenced by several factors, age, amount form diet, lifestyle, genetic background. upper limit normal serum healthy adults approximately 1.5 mg Cu/L, while safe average intake set 10-12 mg/day, reference 0.9 minimum 0.6-0.7 mg/day. essential, optimal dose, provides antioxidant defense, reduces body's ability cope oxidative stress. civilization constant, all electrical devices will not stopped, but health people directly related extraction, production, distribution controlled, inhabitants nearby towns protected. extremely difficult assess on because ubiquity increasing reports about effects, nanoparticles.

Язык: Английский

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