Multi-mechanism antitumor/antibacterial effects of Cu-EGCG self-assembling nanocomposite in tumor nanotherapy and drug-resistant bacterial wound infections

Journal of Colloid and Interface Science, Год журнала: 2024, Номер 671, С. 751 - 769

Опубликована: Май 19, 2024

Язык: Английский

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Therapeutic strategies of targeting non-apoptotic regulated cell death (RCD) with small-molecule compounds in cancer

Acta Pharmaceutica Sinica B, Год журнала: 2024, Номер 14(7), С. 2815 - 2853

Опубликована: Апрель 24, 2024

Regulated cell death (RCD) is a controlled form of orchestrated by one or more cascading signaling pathways, making it amenable to pharmacological intervention. RCD subroutines can be categorized as apoptotic non-apoptotic and play essential roles in maintaining homeostasis, facilitating development, modulating immunity. Accumulating evidence has recently revealed that evasion frequently the primary cause tumor survival. Several have garnered attention promising cancer therapies due their ability induce regression prevent relapse, comparable apoptosis. Moreover, they offer potential solutions for overcoming acquired resistance tumors toward drugs. With an increasing understanding underlying mechanisms governing these subroutines, growing number small-molecule compounds targeting single multiple pathways been discovered, providing novel strategies current therapy. In this review, we comprehensively summarized regulatory emerging mainly including autophagy-dependent death, ferroptosis, cuproptosis, disulfidptosis, necroptosis, pyroptosis, alkaliptosis, oxeiptosis, parthanatos, mitochondrial permeability transition (MPT)-driven necrosis, entotic NETotic lysosome-dependent immunogenic (ICD). Furthermore, focused on discussing related compounds. brief, insightful findings may provide valuable guidance investigating individual collaborative approaches towards different ultimately driving discovery target significantly enhance future therapeutics.

Язык: Английский

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PRDX6 dictates ferroptosis sensitivity by directing cellular selenium utilization

Molecular Cell, Год журнала: 2024, Номер 84(23), С. 4629 - 4644.e9

Опубликована: Ноя. 14, 2024

Selenium-dependent glutathione peroxidase 4 (GPX4) is the guardian of ferroptosis, preventing unrestrained (phospho)lipid peroxidation by reducing phospholipid hydroperoxides (PLOOH). However, contribution other peroxidases in ferroptosis protection remains unclear. We show that cells lacking GPX4 still exhibit substantial PLOOH-reducing capacity, suggesting a alternative PLOOH peroxidases. By scrutinizing potential candidates, we found although overexpression peroxiredoxin 6 (PRDX6), thiol-specific antioxidant enzyme with reported activity, failed to prevent its genetic loss sensitizes cancer ferroptosis. Mechanistically, uncover PRDX6, beyond known acts as selenium-acceptor protein, facilitating intracellular selenium utilization and efficient incorporation into selenoproteins, including GPX4. Its physiological significance was demonstrated reduced expression Prdx6-deficient mouse brains increased sensitivity PRDX6-deficient tumor xenografts mice. Our study highlights PRDX6 critical player directing cellular dictating sensitivity.

Язык: Английский

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Ferroptosis and the tumor microenvironment

Journal of Experimental & Clinical Cancer Research, Год журнала: 2024, Номер 43(1)

Опубликована: Ноя. 30, 2024

Abstract Ferroptosis is a type of regulated cell death characterized by its non-apoptotic, iron-dependent and oxidative nature. Since discovery in 2012, extensive research has demonstrated pivotal roles tumorigenesis, metastasis cancer therapy. The tumor microenvironment (TME) complex ecosystem comprising cells, non-cancer extracellular matrix, metabolites cytokines. Recent studies have underscored new paradigm which cells the TME, such as immune stromal also play significant regulating progression therapeutic resistance typically through complicated crosstalk with cells. Notably, this TME were partially mediated ferrotopsis-related mechanisms. This review provides comprehensive systematic summary current findings concerning ferroptosis how ferroptosis-mediated reprogramming impacts progression. Additionally, outlines various ferroptosis-related strategies aimed at targeting TME.

Язык: Английский

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Downregulation of the SREBP pathways and disruption of redox status by 25-hydroxycholesterol predispose cells to ferroptosis

Free Radical Biology and Medicine, Год журнала: 2025, Номер 228, С. 319 - 328

Опубликована: Янв. 7, 2025

Enzymatically formed side-chain oxysterols function as signaling molecules regulating cholesterol homeostasis and act intermediates in the biosynthesis of bile acids. In addition to these physiological functions, an imbalance oxysterol has been implicated pathophysiology. Cholesterol 25-hydroxylase (CH25H) its product 25-hydroxycholesterol (25-OHC), also by autoxidation, are associated with amyotrophic lateral sclerosis. However, effects 25-OHC on cell viability glial cells remain unclear. This study demonstrates that induces ferroptosis, iron-dependent programmed death, mouse Schwann IMS32 cells. Mechanistically, suppressed expression selenoprotein glutathione peroxidase 4 (GPX4) at both transcriptional translational levels inhibiting processing sterol regulatory element-binding proteins (SREBPs). addition, upregulated NADH-cytochrome b5 reductase 1 (CYB5R1) NADPH-cytochrome P450 (POR), enzymes promote lipid peroxidation. We further found increases glutathione-specific gamma-glutamylcyclotransferase (CHAC1) decreases levels. Importantly, non-cytotoxic concentrations enhanced cellular sensitivity ferroptosis inducers downregulating GPX4 expression. These findings reveal a multifaceted approach whereby through SREBP pathway suppression redox

Язык: Английский

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Camptothecin-based prodrug nanomedicines for cancer therapy

Nanoscale, Год журнала: 2023, Номер 15(44), С. 17658 - 17697

Опубликована: Янв. 1, 2023

Camptothecin (CPT) is a cytotoxic alkaloid that attenuates the replication of cancer cells via blocking DNA topoisomerase 1.

Язык: Английский

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Iron toxicity, ferroptosis and microbiota in Parkinson’s disease: Implications for novel targets

Advances in neurotoxicology, Год журнала: 2024, Номер unknown, С. 105 - 132

Опубликована: Янв. 1, 2024

Язык: Английский

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Emerging trends of phytochemicals as ferroptosis modulators in cancer therapy

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 173, С. 116363 - 116363

Опубликована: Март 12, 2024

Ferroptosis, a novel form of regulated cell death characterized by dependence on iron and lipid peroxidation, has been implicated in wide range clinical conditions including neurological diseases, cardiovascular disorders, acute kidney failure, various types cancer. Therefore, it is critical to suppress cancer progression proliferation. Ferroptosis can be triggered cells some normal synthetic substances, such as erastin, Ras-selective lethal small molecule-3, or pharmaceuticals. Natural bioactive compounds are traditional drug discovery tools, have therapeutically used dietary additives pharmaceutical agents against malignancies. The fact that natural products multiple targets minimal side effects led notable advances anticancer research. Research indicated ferroptosis also induced during treatment. In this review, we focused the most recent developments emerging molecular processes significance To provide new perspectives future development ferroptosis-related medications, summary implications phytochemicals triggering through ROS production ferritinophagy induction variety

Язык: Английский

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STX17-DT facilitates axitinib resistance in renal cell carcinoma by inhibiting mitochondrial ROS accumulation and ferroptosis

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 23, 2025

Язык: Английский

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Gambogenic Acid Suppresses Malignant Progression of Non-Small Cell Lung Cancer via GCH1-Mediated Ferroptosis

Pharmaceuticals, Год журнала: 2025, Номер 18(3), С. 374 - 374

Опубликована: Март 6, 2025

Introduction: Non-small cell lung cancer (NSCLC) is a lethal type of (LC) with 5-year survival rate 19%. Because drug resistance typically develops following chemotherapy, radiotherapy, and immunotherapy, novel NSCLC therapeutic strategy urgently demanded. Gambogenic acid (GNA), major bioactive ingredient isolated from gamboge, has multipotent antitumor effects, although activity against unknown. Methods: CCK8, ethynyl deoxyuridine (EdU), the plate colony formation assay, transwell wound healing (WH) assay were used to study effect GNA on proliferation migration ability NSCLC. Flow cytometry was detect apoptosis cycle. Proteomic analysis LiP-SMap downstream target GNA. Ferroptosis inhibitor ferrostatin-1 ferroptosis. Overexpressing GCH1 for rescue experiment. Subcutaneous tumor pulmonary metastasis in mouse model growth metastasis. Results: The results present showed that inhibited cells dose- time-dependent manner, which arrested cycle G0/G1 phase. In vivo data revealed found significantly expression GTP cyclohydrolase 1 (GCH1). interacted ILE248 ARG249 GCH1. overexpression had similar role ferroptosis restored after treatment. Also, promoted reactive oxygen species (ROS) accumulation, reduced mitochondrial membrane potential. or treatment reversed regulation ROS accumulation potential inhibition. Conclusions: Taken together, these findings confirmed suppressed malignant progression by inducing GCH1-mediated

Язык: Английский

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