Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Jan. 3, 2024

Abstract Zinc metabolism at the cellular level is critical for many biological processes in body. A key observation disruption of homeostasis, often coinciding with disease progression. As an essential factor maintaining equilibrium, zinc has been increasingly spotlighted context development. Extensive research suggests zinc’s involvement promoting malignancy and invasion cancer cells, despite its low tissue concentration. This led to a growing body literature investigating metabolism, particularly functions transporters storage mechanisms during transportation under control two major transporter families: SLC30 (ZnT) excretion SLC39 (ZIP) intake. Additionally, this element predominantly mediated by metallothioneins (MTs). review consolidates knowledge on signaling underscores potential molecular pathways linking progression, special focus cancer. We also compile summary clinical trials involving ions. Given main localization cell membrane, targeted therapies, including small molecules monoclonal antibodies, offers promising avenues future exploration.

Language: Английский

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Mild‐Photothermal Effect Induced High Efficiency Ferroptosis‐Boosted‐Cuproptosis Based on Cu₂O@Mn₃Cu₃O₈ Nanozyme

Advanced Science, Journal Year: 2023, Volume and Issue: 10(33)

Published: Oct. 11, 2023

Abstract A core‐shell‐structured Cu 2 O@Mn 3 O 8 (CMCO) nanozyme is constructed to serve as a tumor microenvironment (TME)‐activated copper ionophore achieve safe and efficient cuproptosis. The Mn shell not only prevents exposure of normal tissues the core reduce systemic toxicity but also exhibits enhanced enzyme‐mimicking activity owing better band continuity near Fermi surface. glutathione oxidase (GSHOx)‐like CMCO depletes (GSH), which diminishes ability chelate ions, thereby exerting inducing cuproptosis in cancer cells. catalase (CAT)‐like catalyzes overexpressed H TME, generating tricarboxylic acid (TCA) cycle enhance More importantly, Fenton‐like reaction based on release ions inactivation peroxidase 4 induced by elimination GSH results ferroptosis, accompanied accumulation lipid peroxidation reactive oxygen species that can cleave stress‐induced heat shock proteins compromise their protective capacity cells further sensitize nanozymes are partially sulfurized hydrogen sulfide colorectal exhibiting excellent photothermal properties activity. mild effect enhances nanozymes, thus high‐efficiency ferroptosis‐boosted‐cuproptosis.

Language: Английский

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Copper and Copper Complexes in Tumor Therapy

ChemMedChem, Journal Year: 2024, Volume and Issue: 19(11)

Published: March 6, 2024

Copper (Cu), a crucial trace element in physiological processes, has garnered significant interest for its involvement cancer progression and potential therapeutic applications. The regulation of cellular copper levels is essential maintaining homeostasis, as imbalances can lead to toxicity cell death. development drugs that target homeostasis emerged promising strategy anticancer treatment, with particular focus on chelators, ionophores, novel complexes. Recent research also investigated the complexes therapy.

Language: Английский

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

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

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Metal ions and nanometallic materials in antitumor immunity: Function, application, and perspective

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: Jan. 19, 2023

The slightest change in the extra/intracellular concentration of metal ions results amplified effects by signaling cascades that regulate both cell fate within tumor microenvironment and immune status, which influences network antitumor immunity through various pathways. Based on fact influence cancer cells participate innate adaptive immunity, they are widely applied therapy as modulators. Moreover, nanomedicine possesses advantage precise delivery responsive release, can perfectly remedy drawbacks ions, such low target selectivity systematic toxicity, thus providing an ideal platform for ion application treatment. Emerging evidence has shown immunotherapy with nanometallic materials may significantly enhance therapeutic efficacy. Here, we focus physiopathology tumorigenesis discuss several breakthroughs regarding use immunotherapeutics. These findings demonstrate prominence ion-based prophylaxis, many new ideas basic research clinical application. Consequently, provide innovative insights into comprehensive understanding combined past few years.

Language: Английский

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Calcium Phosphate-Based Nanomaterials: Preparation, Multifunction, and Application for Bone Tissue Engineering

Molecules, Journal Year: 2023, Volume and Issue: 28(12), P. 4790 - 4790

Published: June 15, 2023

Calcium phosphate is the main inorganic component of bone. phosphate-based biomaterials have demonstrated great potential in bone tissue engineering due to their superior biocompatibility, pH-responsive degradability, excellent osteoinductivity, and similar components nanomaterials gained more attention for enhanced bioactivity better integration with host tissues. Additionally, they can also be easily functionalized metal ions, bioactive molecules/proteins, as well therapeutic drugs; thus, calcium been widely used many other fields, such drug delivery, cancer therapy, nanoprobes bioimaging. Thus, preparation methods were systematically reviewed, multifunction strategies comprehensively summarized. Finally, applications perspectives engineering, including defect repair, regeneration, illustrated discussed by presenting typical examples.

Language: Английский

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Glutathione-responsive and -exhausting metal nanomedicines for robust synergistic cancer therapy

Frontiers in Bioengineering and Biotechnology, Journal Year: 2023, Volume and Issue: 11

Published: March 10, 2023

Due to their rapid and uncontrolled proliferation, cancer cells are characterized by overexpression of glutathione (GSH), which impairs reactive oxygen species (ROS)-based therapy weakens the chemotherapeutic agent-induced toxification. Extensive efforts have been made in past few years improve therapeutic outcomes depleting intracellular GSH. Special focus has given anticancer applications varieties metal nanomedicines with GSH responsiveness exhaustion capacity. In this review, we introduce several GSH-responsive -exhausting that can specifically ablate tumors based on high concentration cells. These include inorganic nanomaterials, metal-organic frameworks (MOFs), platinum-based nanomaterials. We then discuss detail extensively applied synergistic therapy, including chemotherapy, photodynamic (PDT), sonodynamic (SDT), chemodynamic (CDT), ferroptotic radiotherapy. Finally, present horizons challenges field for future development.

Language: Английский

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Polyphyllin I suppresses the gastric cancer growth by promoting cancer cell ferroptosis

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: April 4, 2023

Background: Ferroptosis is a new form of regulated cell death characterized by the accumulation iron-dependent lipid peroxides and membrane damages. Recent studies have identified an important role for cancer ferroptosis in antitumor therapy. On other hand, polyphyllin I (PPI) has been reported to exert effects on some types cancers. However, it remains unknown whether or not PPI regulates ferroptosis. Methods: Two human gastric cells (AGS MKN-45) were used establish tumor xenograft models nude mice that treated with observe growth, while also cultured vitro studies. Ferroptosis, based intracellular ROS/lipid ROS production ferrous ions, was detected using fluorescence microscope flow cytometer, expression NRF2/FTH1 measured Western blotting assays. Results: Here we found inhibited growth vivo increasing reactive oxygen species (ROS)/lipid ions cells. decreased levels nuclear factor erythroid 2-related 2 (NRF2) ferritin heavy chain 1 (FTH1) vitro. Moreover, liproxstain-1, inhibitor ferroptosis, mostly reversed arrest induced PPI. Finally, diminished overexpression NRF2. Conclusion: For first time, our results demonstrated exerts its activity by, at least partially, inducing via regulating pathway. These findings may be implicated clinical replacement therapy cancer.

Language: Английский

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Multiple forms of cell death: A focus on the PI3K/AKT pathway

Journal of Cellular Physiology, Journal Year: 2023, Volume and Issue: 238(9), P. 2026 - 2038

Published: Aug. 10, 2023

Abstract Cell death is a natural biological process that occurs in living organisms. Since 1963, extensive research has shed light on the occurrence, progress, and final outcome of cell death. According to different phenotypes, it classified into types, including apoptosis, pyroptosis, necroptosis, autophagy, ferroptosis, cuproptosis, so on. However, regardless form death, what we ultimately expect disappearance abnormal cells, such as tumor while normal cells survive. As result, vital investigate details triggers, potent regulators, executioners. Although significant progress been made understanding molecular pathways many aspects remain unclear because complex regulatory networks cells. Among them, phosphoinositide‐3‐kinase (PI3K)/protein kinase B(AKT) pathway discovered be crucial regulator process. AKT, proto‐oncogene, become major focus attention medical community due its role regulating multiplicity cellular functions counting metabolism, immunity, proliferation, survival, transcription, protein synthesis. Here, explored connection between PI3K/AKT aiming enhance our comprehension mechanism underlying this Such knowledge may pave way for subsequent development more effective disease treatments, finding suitable targets drug intervention.

Language: Английский

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From ferroptosis to cuproptosis, and calcicoptosis, to find more novel metals-mediated distinct form of regulated cell death

APOPTOSIS, Journal Year: 2024, Volume and Issue: 29(5-6), P. 586 - 604

Published: Feb. 7, 2024

Language: Английский

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