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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Ferroptosis as a potential target for cancer therapy

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(7)

Published: July 24, 2023

Abstract Ferroptosis is a recently discovered essential type of cell death that mainly characterized by iron overload and lipid peroxidation. Emerging evidence suggests ferroptosis double-edged sword in human cancer. However, the precise underlying molecular mechanisms their differential roles tumorigenesis are unclear. Therefore, this review, we summarize briefly present key pathways ferroptosis, paying special attention to regulation as well its dual role an oncogenic tumor suppressor event various cancers. Moreover, multiple pharmacological activators summarized, prospect targeting cancer therapy further elucidated.

Language: Английский

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Neoadjuvant apatinib addition to sintilimab and carboplatin-taxane based chemotherapy in patients with early triple-negative breast cancer: the phase 2 NeoSAC trial

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 6, 2025

Abstract We aimed to evaluate the efficacy and safety of adding apatinib, sintilimab chemotherapy in neoadjuvant treatment early triple-negative breast cancer (TNBC). In phase 2 NeoSAC trial, patients with TNBC received six cycles sintilimab, nab-paclitaxel, carboplatin followed by surgery. The primary endpoint was pathological complete response (pCR) rate. Specimens collected pre-neoadjuvant therapy post-surgery were retained for comprehensive analysis predictive biomarkers impact on tumor microenvironment. Among 34 enrolled patients, 24 achieved pCR (70.6%; 95% confidence interval (CI), 53.0-85.3), 79.4% (95% CI, 65.1-93.7) had residual burden 0-I. Imaging evaluation showed 21 responses (61.8%) 13 partial (38.2%). most common grade 3-4 adverse events leukopenia (47%), neutropenia (36%), thrombocytopenia (24%). 36-month disease-free survival rate stood at 94.1% a median follow-up 39.1 months. Notably, baseline high ImmuneScore, immune cell infiltration, enrichment interferon-related pathways correlated pCR. Comparison data revealed that group treated this novel regimen exhibited an upregulation distinct subsets, thereby activating Moreover, higher oxeiptosis scores associated increased likelihood achieving Following therapy, decrease score, whereas non-pCR increase. Our study suggests combined nab-paclitaxel promising clinical activity manageable profile merits further study. ClinicalTrials.gov registration: NCT04722718.

Language: Английский

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Regulated cell death in glioma: promising targets for natural small-molecule compounds

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 18, 2024

Gliomas are prevalent malignant tumors in adults, which can be categorized as either localized or diffuse gliomas. Glioblastoma is the most aggressive and deadliest form of glioma. Currently, there no complete cure, median survival time less than one year. The main mechanism regulated cell death involves organisms coordinating elimination damaged cells at risk tumor transformation hijacked by microorganisms for pathogen replication. This process includes apoptosis, necroptosis, autophagy, ferroptosis, pyroptosis, necrosis, parthanayosis, entosis, lysosome-dependent death, NETosis, oxiptosis, alkaliptosis, disulfidaptosis. goal clinical oncology to develop therapies that promote effective cancer regulating oncology. Recently, scientists have utilized pertinent regulatory factors natural small-molecule compounds induce treatment By analyzing PubMed Web Science databases, this paper reviews research progress on regulation role aim provide help glioblastoma.

Language: Английский

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Mitoquinone shifts energy metabolism to reduce ROS-induced oxeiptosis in female granulosa cells and mouse oocytes

Aging, Journal Year: 2023, Volume and Issue: 15(1), P. 246 - 260

Published: Jan. 9, 2023

The female reproductive system is quite sensitive to regulation, and external environmental stimuli may cause oxidative stress which in turn lead accelerated aging programmed cell death cells. aim of this study was investigate whether or not mitoquinone (MitoQ) could resist ROS-induced apoptosis human granulosa cells mouse oocytes. We found that the MitoQ treatment significantly reduced production reactive oxygen species (ROS) imbalance mitochondrial membrane potential. prevented an excessive fragmentation by upregulating Drp1 S637 decreasing phosphorylation. More importantly, maintained aerobic respiration anaerobic regulating reprogramming intracellular energy metabolism, enhanced cellular ATP production. effectively expressions AIFM1 PGAM5, key molecules whose were reversed only but also Our findings suggest can ameliorate deterioration caused ROS reprogram providing protection against apoptosis. presence help protecting germ under vitro culture conditions.

Language: Английский

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Ferroptosis is an effective strategy for cancer therapy

Medical Oncology, Journal Year: 2024, Volume and Issue: 41(5)

Published: April 23, 2024

Language: Английский

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Upregulation of the ferroptosis-related STEAP3 gene is a specific predictor of poor triple-negative breast cancer patient outcomes

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: March 31, 2023

This study was designed to assess ferroptosis regulator gene (FRG) expression patterns in patients with TNBC based on data derived from The Cancer Genome Atlas (TCGA). Further, it utilized establish a FRG signature, after which the association between this signature and tumor immune microenvironment (TIME) composition assessed, relevant prognostic factors were explored.The TCGA database used obtain RNA datasets clinical information about 190 patients, TNBC-related established using least absolute shrinkage selection operator (LASSO) Cox regression approach. These results validated separate Gene Expression Omnibus (GEO). TNBC-specific identified via method. STEAP3 then through Western immunoblotting, immunohistochemical staining, quantitative real-time polymerase chain reaction (RT-qPCR) analyses of tissue samples cell lines. Chemotherapy interactions predicted drug sensitivity studies investigated learn more potential relevance these observations.These revealed that 87 FRGs differentially expressed when comparing tumors healthy (87/259, 33.59%). Seven genes (CA9, CISD1, STEAP3, HMOX1, DUSP1, TAZ, HBA1) are significantly related overall survival patients. Kaplan-Meier signatures nomograms CISD1 relevance. Prognostic Risk Score values positively correlated infiltration CD4+ T cells (p = 0.001) myeloid dendritic =0.004). Further evidence showed strongly specifically associated patient OS (P<0.05). above confirmed by additional examinations changes High levels negatively half-maximal inhibitory concentration (IC50) for GSK1904529A (IGF1R inhibitor), AS601245 (JNK XMD8-85 (Erk5 Gefitinib, Sorafenib, 5-Fluorouracil (P < 0.05) TCGA-TNBC dataset.In present study, novel model developed forecast prognosis accurately. Furthermore, discovered highly overexpressed people rates, laying groundwork eventually targeted therapy individuals form cancer.

Language: Английский

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Mitochondrial Regulation of Ferroptosis in Cancer Therapy

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(12), P. 10037 - 10037

Published: June 12, 2023

Ferroptosis, characterized by glutamate overload, glutathione depletion, and cysteine/cystine deprivation during iron- oxidative-damage-dependent cell death, is a particular mode of regulated death. It expected to effectively treat cancer through its tumor-suppressor function, as mitochondria are the intracellular energy factory binding site reactive oxygen species production, closely related ferroptosis. This review summarizes relevant research on mechanisms ferroptosis, highlights mitochondria's role in it, collects classifies inducers A deeper understanding relationship between ferroptosis mitochondrial function may provide new strategies for tumor treatment drug development based

Language: Английский

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Polystyrene nanoplastics induce haematotoxicity with cell oxeiptosis and senescence involved in C57BL/6J mice

Environmental Toxicology, Journal Year: 2023, Volume and Issue: 38(10), P. 2487 - 2498

Published: July 19, 2023

Nanoplastics (NPs) has become a worrying serious environmental problem. However, the toxicological effects and mechanisms of NPs on hematopoiesis are still unknown. To this end, male C57BL/6J mice were directly exposed to serial concentration gradient polystyrene (PSNPs, 0, 30, 60, 120 μg d), respectively, for 42 days by intragastric administration. Results show that PSNPs clearly visible in bone tissues, meanwhile, induced count major blood indicators (WBC, RBC, LYM) decreased. H&E staining displayed can cause hematopoietic damage BM extramedullary spleen. Flow cytometry result proportion LSK represented dose-dependent significantly decreased after exposure. Further research found systemic oxidative stress occurs manifested as MDA accumulated. In addition, dose increased, fluorescence intensity Keap1 p53 femur sections gradually expression cell oxeiptosis signal pathway Keap1/PGAM5/AIFM1 senescence p53/p21 was all markedly. Overall, our study demonstrated exposure caused stress, potentially resulting develop haematotoxicity mice.

Language: Английский

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Ferroptosis induction via targeting metabolic alterations in triple-negative breast cancer

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 169, P. 115866 - 115866

Published: Nov. 10, 2023

Triple-negative breast cancer (TNBC), the most aggressive form of cancer, presents severe threats to women's health. Therefore, it is critical find novel treatment approaches. Ferroptosis, a newly identified programmed cell death, marked by buildup lipid reactive oxygen species (ROS) and high iron concentrations. According previous studies, ferroptosis sensitivity can be controlled number metabolic events in cells, such as amino acid metabolism, metabolism. Given that TNBC tumors are rich lipids, inducing these potential approach for treatment. Notably, adaptability cells allows them coordinate an attack on one or more pathways initiate ferroptosis, offering perspective improve drug resistance clinical therapy TNBC. However, clear picture still needs completely revealed. In this review, we provide overview recent advancements regarding connection between acid, iron, metabolism We also discuss probable significance innovative target chemotherapy, radiotherapy, immunotherapy, nanotherapy natural product TNBC, highlighting its therapeutic application prospects.

Language: Английский

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