System Xc−/GSH/GPX4 axis: An important antioxidant system for the ferroptosis in drug-resistant solid tumor therapy

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

Published: Aug. 29, 2022

The activation of ferroptosis is a new effective way to treat drug-resistant solid tumors. Ferroptosis an iron-mediated form cell death caused by the accumulation lipid peroxides. intracellular imbalance between oxidant and antioxidant due abnormal expression multiple redox active enzymes will promote produce reactive oxygen species (ROS). So far, few pathways regulators have been discovered regulate ferroptosis. In particular, cystine/glutamate antiporter (System X c − ), glutathione peroxidase 4 (GPX4) (GSH) /GSH/GPX4 axis) plays key role in preventing peroxidation-mediated ferroptosis, because which could be inhibited blocking System axis. This review aims present current understanding mechanism based on axis treatment

Language: Английский

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PANoptosis: A Unique Innate Immune Inflammatory Cell Death Modality

The Journal of Immunology, Journal Year: 2022, Volume and Issue: 209(9), P. 1625 - 1633

Published: Oct. 20, 2022

Abstract Innate immunity is the first response to protect against pathogens and cellular insults. Pattern recognition receptors sense pathogen- damage-associated molecular patterns induce an innate immune characterized by inflammation programmed cell death (PCD). In-depth characterization of PCD pathways has highlighted significant cross-talk. Recent advances led identification a unique inflammatory modality called PANoptosis, which regulated multifaceted PANoptosome complexes that are assembled integrating components from other pathways. The totality biological effects observed in PANoptosis cannot be accounted for any pathway alone. In this review, we briefly describe mechanisms death, including activation regulation. We also highlight PANoptosomes identified date provide overview implications disease therapeutic targeting. Improved understanding immune-mediated critical inform next generation treatment strategies.

Language: Английский

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Advances in mechanism and regulation of PANoptosis: Prospects in disease treatment

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

Published: Feb. 9, 2023

PANoptosis, a new research hotspot at the moment, is cell death pattern in which pyroptosis, apoptosis, and necroptosis all occur same population. In essence, PANoptosis highly coordinated dynamically balanced programmed inflammatory pathway that combines main features of necroptosis. Many variables, such as infection, injury, or self-defect, may be involved occurrence with assembly activation PANoptosome being most critical. has been linked to development multiple systemic diseases human body, including infectious diseases, cancer, neurodegenerative diseases. Therefore, it necessary clarify process occurrence, regulatory mechanism its relation this paper, we summarized differences relations between three types death, emphatically expounded molecular patterns expectation facilitating application regulation disease treatment.

Language: Английский

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Self‐Destructive Copper Carriers Induce Pyroptosis and Cuproptosis for Efficient Tumor Immunotherapy Against Dormant and Recurrent Tumors

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(8)

Published: Oct. 11, 2023

Abstract Activating the strong immune system is a key initiative to counteract dormant tumors and prevent recurrence. Herein, self‐destructive multienzymatically active copper‐quinone‐GOx nanoparticles (abbreviated as CQG NPs) have been designed induce harmonious balanced pyroptosis cuproptosis using “Tai Chi mindset” awaken response for suppressing recurrent tumors. This cleverly material can disrupt antioxidant defense mechanism of tumor cells by inhibiting nuclear factor‐erythroid 2‐related factor 2 (NRF2)‐quinone oxidoreductase 1 (NQO1) signaling pathway. Furthermore, combined with its excellent multienzyme activity, it activates NOD‐like receptor protein 3 (NLRP3)‐mediated pyroptosis. Meanwhile, be triggered copper ions released from disintegration NPs sensitivity cancer enhanced through depletion endogenous chelators via Michael addition reaction between glutathione (GSH) quinone ligand, oxygen production catalase‐like reaction, starvation‐induced glucose deficiency. More importantly, NPs‐induced promote immunosuppressive microenvironment (TME) remodeling, enhance infiltration into tumor, activate robust systemic immunity. Collectively, this study provides new strategy resist dormancy, recurrence, improve clinical prognosis

Language: Английский

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PANoptosis: A Cell Death Characterized by Pyroptosis, Apoptosis, and Necroptosis

Journal of Inflammation Research, Journal Year: 2023, Volume and Issue: Volume 16, P. 1523 - 1532

Published: April 1, 2023

Abstract: PANoptosis is a new cell death proposed by Malireddi et al in 2019, which characterized pyroptosis, apoptosis and necroptosis, but cannot be explained any of them alone. The interaction between necroptosis involved PANoptosis. In this review, from the perspective PANoptosis, we focus on relationship key molecules process formation PANoptosome, as well role diseases. We aim to understand mechanism provide basis for targeted intervention PANoptosis-related treat human Keywords: apoptosis,

Language: Английский

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Iron and copper: critical executioners of ferroptosis, cuproptosis and other forms of cell death

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Nov. 16, 2023

Abstract Regulated cell death (RCD) is a regulable that involves well-organized signaling cascades and molecular mechanisms. RCD implicated in fundamental processes such as organ production tissue remodeling, removing superfluous structures or cells, regulating numbers. Previous studies have not been able to reveal the complete mechanisms, novel methods of are constantly being proposed. Two metal ions, iron (Fe) copper (Cu) essential factors leading RCDs only induce ferroptosis cuproptosis, respectively but also lead impairment eventually diverse death. This review summarizes direct indirect mechanisms by which Fe Cu impede growth various forms mediated these two metals. Moreover, we aimed delineate interrelationships between with distinct pathways shedding light on complex intricate govern cellular survival Finally, prospects outlined this suggest approach for investigating death, may involve integrating current therapeutic strategies offer promising solution overcome drug resistance certain diseases.

Language: Английский

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PANoptosis: Mechanisms, biology, and role in disease

Immunological Reviews, Journal Year: 2023, Volume and Issue: 321(1), P. 246 - 262

Published: Oct. 12, 2023

Summary Cell death can be executed through distinct subroutines. PANoptosis is a unique inflammatory cell modality involving the interactions between pyroptosis, apoptosis, and necroptosis, which mediated by multifaceted PANoptosome complexes assembled via integrating components from other modalities. There growing interest in process function of PANoptosis. Accumulating evidence suggests that occurs under diverse stimuli, for example, viral or bacterial infection, cytokine storm, cancer. Given impact across disease spectrum, this review briefly describes relationships highlights key molecules formation activation, outlines roles diseases together with potential therapeutic targeting. We also discuss important concepts pressing issues future research. Improved understanding its mechanisms crucial identifying novel targets strategies.

Language: Английский

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Immunogenic PANoptosis‐Initiated Cancer Sono‐Immune Reediting Nanotherapy by Iteratively Boosting Cancer Immunity Cycle

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(2)

Published: Sept. 13, 2023

Abstract The cancer‐immune cycle conceptualized the mechanisms of driving T cell responses to tumors, but w as limited by immunological ignorance elicited tumor inherent immunoediting, which failed initiate and maintain adaptive immunity. Targeting specific vulnerabilities death patterns may provide unique opportunities boost antitumor effects. Here an ultrasound nanomedicine‐triggered immuno‐reediting therapeutic strategy using nano/genetically engineered extracellular vesicles, can induce highly immunogenic PANoptosis iteratively start‐up energization cancer innate immunity repeatedly liberating damage‐associated molecular patterns, thereby priming sufficient antigen‐specific cells shaping protective immune response through activating cGAS‐STING signaling pathways, is reported. Aided checkpoint blockade, reprogramming microenvironment further facilitated a prompt bridging immunity, remarkably suppressed metastatic rechallenged growth. Thus, targeting PANoptotic provides catcher against escape positive‐feedback activation gateway for overcoming resistance intractable cancers.

Language: Английский

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Sulconazole Induces PANoptosis by Triggering Oxidative Stress and Inhibiting Glycolysis to Increase Radiosensitivity in Esophageal Cancer

Molecular & Cellular Proteomics, Journal Year: 2023, Volume and Issue: 22(6), P. 100551 - 100551

Published: April 18, 2023

Esophageal cancer is the seventh most common in world. Although traditional treatment methods such as radiotherapy and chemotherapy have good effects, their side effects drug resistance remain problematic. The repositioning of function provides new ideas for research development anticancer drugs. We previously showed that Food Drug Administration-approved sulconazole can effectively inhibit growth esophageal cells, but its molecular mechanism not clear. Here, our study demonstrated had a broad spectrum effects. It only proliferation also migration cells. Both transcriptomic sequencing proteomic could promote various types programmed cell death glycolysis related pathways. Experimentally, we found induced apoptosis, pyroptosis, necroptosis, ferroptosis. Mechanistically, triggered mitochondrial oxidative stress inhibited glycolysis. Finally, low-dose increase radiosensitivity Taken together, these findings provide strong laboratory evidence clinical application cancer.

Language: Английский

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Mechanisms of PANoptosis and relevant small-molecule compounds for fighting diseases

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(12)

Published: Dec. 21, 2023

Abstract Pyroptosis, apoptosis, and necroptosis are mainly programmed cell death (PCD) pathways for host defense homeostasis. PANoptosis is a newly distinct inflammatory PCD pathway that uniquely regulated by multifaceted PANoptosome complexes highlights significant crosstalk coordination among pyroptosis (P), apoptosis (A), and/or necroptosis(N). Although some studies have focused on the possible role of PANpoptosis in diseases, pathogenesis complex underestimated. Furthermore, progress related agonists or inhibitors disorders has not yet been thoroughly discussed. In this perspective, we provide perspectives context diverse pathological conditions human diseases. The treatment targeting also summarized. conclusion, involved plenty including but limited to microbial infections, cancers, acute lung injury/acute respiratory distress syndrome (ALI/ARDS), ischemia-reperfusion, organic failure. seems be double-edged sword conditions, as induces negative impact prognosis like COVID-19 ALI/ARDS, while provides protection from HSV1 Francisella novicida infection, kills cancer cells suppresses tumor growth colorectal cancer, adrenocortical carcinoma, other cancers. Compounds endogenous molecules promising therapeutic strategies, which can act PANoptosomes-associated members regulate PANoptosis. More researches needed better understand pathology develop treatment.

Language: Английский

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