Mechanism of metal ion-induced cell death in gastrointestinal cancer

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 174, С. 116574 - 116574

Опубликована: Апрель 8, 2024

Gastrointestinal (GI) cancer is one of the most severe types cancer, with a significant impact on human health worldwide. Due to urgent demand for more effective therapeutic strategies against GI cancers, novel research metal ions treating cancers has attracted increasing attention. Currently, accumulating relationship between and therapy, several have been discovered induce cell death. In particular, three modes death, including ferroptosis, cuproptosis, calcicoptosis, become focal points in field cancer. Meanwhile, other also found trigger death through various mechanisms. Accordingly, this review focuses mechanisms ion-induced hoping provide theoretical support further therapies.

Язык: Английский

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Lysosomal Ion Channels and Transporters: Recent Findings, Therapeutic Potential, and Technical Approaches

Bioelectricity, Год журнала: 2025, Номер 7(1), С. 29 - 57

Опубликована: Март 1, 2025

In recent years, there has been a growing interest in lysosomal ion channels and transporters due to their critical role maintaining function involvement variety of diseases, particularly storage cancer, neurodegenerative disorders. Recent advancements research techniques, including manual automated patch clamp (APC) electrophysiology, solid-supported membrane-based electrophysiology (SSME), fluorescence-based imaging, have further enhanced our ability investigate both physiological pathological conditions, spurring drug discovery efforts. Several pharmaceutical companies are now developing therapies aimed at modulating these improve disease. Small molecules targeting like transient receptor potential mucolipin (TRPML) 1 TMEM175, as well drugs pH, currently preclinical clinical development. This review provides an overview the health disease, highlights cutting-edge techniques used study them, discusses therapeutic treatment various diseases. Furthermore, addition summarizing discoveries, we contribute novel functional data on cystinosin, TRPML1, two-pore channel 2 (TPC2), utilizing SSME APC approaches.

Язык: Английский

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Dual inhibition of MYC and SLC39A10 by a novel natural product STAT3 inhibitor derived from Chaetomium globosum suppresses tumor growth and metastasis in gastric cancer

Pharmacological Research, Год журнала: 2023, Номер 189, С. 106703 - 106703

Опубликована: Фев. 17, 2023

Gastric cancer remains one of the most common deadly diseases and lacks effective targeted therapies. In present study, we confirmed that signal transducer activator transcription 3 (STAT3) is highly expressed associated with a poor prognosis in gastric cancer. We further identified novel natural product inhibitor STAT3, termed XYA-2, which interacts specifically SH2 domain STAT3 (Kd = 3.29 μM) inhibits IL-6-induced phosphorylation at Tyr705 nuclear translocation. XYA-2 inhibited viability seven human cell lines 72-h IC50 values ranging from 0.5 to 0.7 μΜ. 1 μΜ colony formation migration ability MGC803 (72.6% 67.6%, respectively) MKN28 (78.5% 96.6%, cells. vivo studies, intraperitoneal administration (10 mg/kg/day, 7 days/week) significantly suppressed 59.8% 88.8% tumor growth MKN28-derived xenograft mouse model MGC803-derived orthotopic model, respectively. Similar results were obtained patient-derived (PDX) model. Moreover, treatment extended survival mice bearing PDX tumors. The molecular mechanism studies based on transcriptomics proteomics analyses indicated might exert its anticancer activity by synergistically inhibiting expression MYC SLC39A10, two downstream genes vitro vivo. Together, these findings suggested may be potent for treating cancer, dual inhibition SLC39A10 an therapeutic strategy STAT3-activated

Язык: Английский

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Advances in Nanodelivery Systems Based on Metabolism Reprogramming Strategies for Enhanced Tumor Therapy

ACS Applied Materials & Interfaces, Год журнала: 2024, Номер 16(6), С. 6689 - 6708

Опубликована: Фев. 1, 2024

Tumor development and metastasis are closely related to the complexity of metabolism network. Recently, reprogramming strategies have attracted much attention in tumor therapy. Although there is preliminary success therapy agents, their therapeutic effects been restricted by effective reaching sites drugs. Nanodelivery systems with unique physical properties elaborate designs can specifically deliver tumors. In this review, we first summarize research progress nanodelivery based on enhance therapies depleting glucose, inhibiting glycolysis, lactic acid, lipid metabolism, glutamine glutathione, disrupting metal metabolisms combined other therapies, including chemotherapy, radiotherapy, photodynamic therapy, etc. We further discuss detail advantages for As well as opportunities challenges integrating into analyze outlook these emerging areas. This review expected improve our understanding modulating enhanced

Язык: Английский

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Zinc oxide nanoparticle causes toxicity to the development of mouse oocyte and early embryo

Toxicology Letters, Год журнала: 2022, Номер 358, С. 48 - 58

Опубликована: Янв. 21, 2022

Язык: Английский

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Die hard: cell death mechanisms and their implications in nanotoxicology

Toxicological Sciences, Год журнала: 2023, Номер 192(2), С. 141 - 154

Опубликована: Фев. 8, 2023

Abstract Cell death is a fundamental biological process, and its fine-tuned regulation required for life. However, the complexity of regulated cell often reduced to matter live-dead discrimination. Here, we provide perspective on programmed or death, focusing apoptosis, pyroptosis, necroptosis, ferroptosis (the latter three modalities are examples necrosis). We also touch other, recently described manifestations (pathological) including cuproptosis. Furthermore, address how engineered nanomaterials impact death. posit that an improved understanding nanomaterial-induced perturbations may allow better prediction consequences human exposure these materials could yield novel approaches by which mitigate their effects. Finally, harnessing achieve cancer killing through induction

Язык: Английский

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Contribution of zinc accumulation to ischemic brain injury and its mechanisms about oxidative stress, inflammation, and autophagy: an update

Metallomics, Год журнала: 2024, Номер 16(3)

Опубликована: Фев. 28, 2024

Abstract Ischemic stroke is a leading cause of death and disability worldwide, presently, there no effective neuroprotective therapy. Zinc an essential trace element that plays important physiological roles in the central nervous system. Free zinc concentration tightly regulated by zinc-related proteins brain under normal conditions. Disruption homeostasis, however, has been found to play role mechanism injury following ischemic stroke. A large free releases from storage sites after cerebral ischemia, which affects functions survival nerve cells, including neurons, astrocytes, microglia, resulting cell death. Ischemia-triggered intracellular accumulation also disrupts function blood–brain barrier via increasing its permeability, impairing endothelial function, altering tight junction levels. Oxidative stress neuroinflammation have reported be as major pathological mechanisms ischemia/reperfusion injury. Studies showed could impair mitochondrial result oxidative stress, form positive feedback loop between reactive oxygen species production, leads series harmful reactions. Meanwhile, elevated neuroinflammation. Recent studies autophagy one toxicity Interrupting will reduce ischemia improve neurological outcomes. This review summarizes cellular tissue damage focusing on about inflammation, autophagy.

Язык: Английский

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Targeting lysosomal quality control as a therapeutic strategy against aging and diseases

Medicinal Research Reviews, Год журнала: 2024, Номер 44(6), С. 2472 - 2509

Опубликована: Май 6, 2024

Previously, lysosomes were primarily referred to as the digestive organelles and recycling centers within cells. Recent discoveries have expanded lysosomal functional scope revealed their critical roles in nutrient sensing, epigenetic regulation, plasma membrane repair, lipid transport, ion homeostasis, cellular stress response. Lysosomal dysfunction is also found be associated with aging several diseases. Therefore, function of macroautophagy, a lysosome-dependent intracellular degradation system, has been identified one updated twelve hallmarks aging. In this review, we begin by introducing concept quality control (LQC), which machinery that maintains number, morphology, through different processes such biogenesis, reformation, fission, fusion, turnover, lysophagy, exocytosis, permeabilization repair. Next, summarize results from studies reporting association between LQC dysregulation aging/various disorders. Subsequently, explore emerging therapeutic strategies target distinct aspects for treating diseases combatting Lastly, underscore existing knowledge gap propose potential avenues future research.

Язык: Английский

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Mechanisms and therapeutic potential of disulphidptosis in cancer

Cell Proliferation, Год журнала: 2024, Номер unknown

Опубликована: Окт. 1, 2024

Abstract SLC7A11 plays a pivotal role in tumour development by facilitating cystine import to enhance glutathione synthesis and counteract oxidative stress. Disulphidptosis, an emerging form of cell death observed cells with high expression under glucose deprivation, is regulated through reduction–oxidation reactions disulphide bond formation. This process leads contraction collapse the F‐actin cytoskeleton from plasma membrane, ultimately resulting cellular demise. Compared other forms death, disulphidptosis exhibits distinctive characteristics regulatory mechanisms. mechanism provides novel insights innovative strategies for cancer treatment while also inspiring potential therapeutic approaches diseases. Our review focuses on elucidating molecular underlying its connection actin cytoskeleton, identifying alternative metabolic as well offering into disulphidptosis‐based therapy. A comprehensive understanding will contribute our knowledge about fundamental homeostasis facilitate groundbreaking therapies disease treatment.

Язык: Английский

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Lucanthone, a Potential PPT1 inhibitor, Perturbs Stemness, Reduces Tumor Microtube Formation and Slows the Growth of Temozolomide-Resistant Gliomas in Vivo

Journal of Pharmacology and Experimental Therapeutics, Год журнала: 2024, Номер unknown, С. JPET - 002021

Опубликована: Янв. 31, 2024

Glioblastoma (GBM) is the most frequently diagnosed primary central nervous system tumor in adults. Despite standard of care therapy, which includes surgical resection, temozolomide chemotherapy, radiation and newly added tumor-treating fields, median survival remains only ∼20 months. Unfortunately, GBM has a ∼100% recurrence rate, but after there are no Food Drug Administration-approved therapies to limit growth enhance patient survival, as these tumors resistant (TMZ). Recently, our laboratory reported that lucanthone slows by inhibiting autophagic flux through lysosome targeting decreases number Olig2+ glioma stem-like cells (GSC) vitro vivo. We now additionally report efficiently abates stemness patient-derived GSC reduces microtube formation GSC, an emerging hallmark treatment resistance GBM. In derived from with acquired TMZ, retains ability perturb growth, inhibits autophagy lysosomes, Olig2 positivity. also find may act inhibitor palmitoyl protein thioesterase 1. Our results suggest function potential option for not amenable TMZ treatment.

SIGNIFICANCE STATEMENT

antischistosome agent impedes preclinical model temozolomide-resistant glioblastoma numbers cells. addition, it acts inhibitor, its mechanism action be via inhibition As defined approved recurrent, TMZ-resistant tumor, could emerge both recurrent settings.

Язык: Английский

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