Ferroptosis and immunosenescence in colorectal cancer

Seminars in Cancer Biology, Journal Year: 2024, Volume and Issue: 106-107, P. 156 - 165

Published: Oct. 16, 2024

Language: Английский

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Dual‐Release Free Iron and Breakdown of Ferroptosis Defenses to Achieve Ferroptosis Cascade Storms for Potent Antitumor Therapy

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 19, 2025

Abstract Ferroptosis is a newly identified type of regulated cell death characterized by iron‐dependent lipid peroxidation. Among the main ferroptosis‐suppressing systems, dihydroorotate dehydrogenase (DHODH)‐ ubiquinone axis closely related to mitochondria and energy metabolism, implying that protects cells from oxidative stress damage via maintenance redox homeostasis. However, ferroptosis initiation requires suitable environment breakthrough in homeostatic limitations systems. Hence, nanoparticles are rationally engineered achieve efficient induction releasing dual‐release free iron disrupting Atovaquone (ATO)‐loaded hollow mesoporous etching zeolitic imidazolate framework‐67 double‐coated oxide/calcium phosphate (Fe 3 O 4 /CaP) conjugated with polyethylene glycol. The external Fe /CaP structure enhances efficiency multiple reactive oxygen species (ROS) generation promoting stress. Still, it achieves increase content unstable pools for igniting ROS storm peroxidation spark. release ATO not only affects metabolism mitochondrial respiratory chain binding complex III but also downregulates DHODH restrict ubiquinol system disrupt Therefore, design this composite nanomedicine provides an approach inducing theoretical basis clinical anti‐tumor trials.

Language: Английский

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Absence of Cysteine and Iron Chelation Induces Ferroptosis in Triple-Negative Breast Cancer Cells

Breast Cancer Basic and Clinical Research, Journal Year: 2025, Volume and Issue: 19

Published: Jan. 1, 2025

Background: Ferroptosis is a recently studied form of programmed cell death characterized by lipid peroxides accumulation in the cells. This process occurs when cell’s antioxidant capacity disturbed resulting inability to detoxify toxic peroxides. Two major components that regulate ferroptosis are cysteine and iron. Objective: study aimed determine effect deficiency iron chelation on triple-negative breast cancer (TNBC) lipid-enriched microenvironment. Design: The has laboratory-based experimental design. used MDA-MB-231 line various vitro culture systems investigate research question. Methods: For first part study, we subjected cells grow cysteine-absent adipocyte-conditioned media. In second half, treated with chelator, deferoxamine. BODIPY imaging western blot were carried out observe under 2 conditions. Results: results showed absence conditioned media was able reduce formation droplets, which increased greater access free fatty acids undergo oxidation, therefore inducing ferroptosis. On contrary, deferoxamine along erastin (ferroptosis-inducing drug), an increase content observed, later Conclusion: Our show alternative function deferoxamine, one regulating droplets other ferroptosis, although inhibitor same, respectively.

Language: Английский

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Unusual chaetoglobosins and a new type of ferroptosis inducer from an endophytic fungus Chaetomium sp. UJN-EF006

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 158, P. 108342 - 108342

Published: March 6, 2025

Language: Английский

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Exploring cell death pathways in oral cancer: mechanisms, therapeutic strategies, and future perspectives

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 26, 2025

Oral squamous cell carcinoma (OSCC) represents a significant global health challenge, characterized by aggressive progression and poor therapeutic response despite advances in treatment modalities. This review provides comprehensive analysis of diverse death mechanisms OSCC, encompassing traditional pathways (apoptosis, autophagy, necrosis), newly (ferroptosis, pyroptosis, necroptosis), emerging (cuproptosis, anoikis, parthanatos, entosis). By examining the molecular basis these pathways, particularly crucial roles p53 signaling miRNA regulation, we highlight how their dysregulation contributes to resistance tumor progression. The synthesizes recent evidence demonstrating complex interplay between ten distinct impact on microenvironment immune response. We evaluate innovative approaches that target including novel small molecules, combination strategies, immunomodulatory treatments exploit specific enhance efficacy. Special attention is given personalized medicine strategies consider individual characteristics pathway profiles. integrating current challenges with future research directions, this framework for developing more effective can leverage multiple overcome therapy improve outcomes oral cancer patients.

Language: Английский

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Cold atmospheric plasma drives USP49/HDAC3 axis mediated ferroptosis as a novel therapeutic strategy in endometrial cancer via reinforcing lactylation dependent p53 expression

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 15, 2025

Endometrial cancer ranks among the most common gynecological cancers, with increasing rates of incidence and death. Cold atmospheric plasma (CAP) has become a promising novel therapeutic approach for treatment. Nevertheless, specific impact CAP on endometrial remains inadequately characterized. This study aimed to investigate effect progression reveal its regulatory mechanisms. Colony formation, EdU, wound-healing, transwell assay were used detect progression. Proteomics is employed identify potential targets signaling pathways through which impacts cells. MDA, lipid ROS, JC-1 MMP assays ferroptosis. Immunoprecipitation-mass spectrometry, co-immunoprecipitation, immunofluorescence co-localization, molecular docking analyze USP49 HDAC3 interactions. The tumor xenografts model determined that inhibits growth in vivo. observed significant inhibitory proliferation migration cells reported first time induces ferroptosis Mechanistically, activated transcription p53 by modulating mediated histone H3K18 lactylation, resulting upregulation driving cell interaction between was validated mass spectrometry co-immunoprecipitation experiments. regulation contingent upon USP49, wherein down-regulation augments ubiquitination HDAC3, consequently diminishing protein stability. Furthermore, animal models transplanted tumors corroborated Our findings illustrate suppressive treatment uncover mechanism CAP. Specifically, modulates pathway HDAC3/H3K18la/p53 axis, presenting

Language: Английский

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Optimizing chemotherapeutic targets in non-small cell lung cancer with transfer learning for precision medicine

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(4), P. e0319499 - e0319499

Published: April 29, 2025

Non-small cell lung cancer (NSCLC) accounts for the majority of cases, making it most fatal diseases worldwide. Predicting NSCLC patients’ survival outcomes accurately remains a significant challenge despite advancements in treatment. The difficulties developing effective drug therapies, which are frequently hampered by severe side effects, resistance, and limited effectiveness across diverse patient populations, highlight complexity NSCLC. machine learning (ML) deep (DL) modelsare starting to reform field disclosure. These methodologies empower distinguishing proof medication targets improvement customized treatment techniques that might actually upgrade endurance results patients. Using cutting-edge methods feature extraction transfer learning, we present discovery model identification therapeutic this paper. For purpose extracting features from protein sequences, make use hybrid UNet transformer. This makes possible extract address issue false alarms. dimensionality reduction, modified Rime optimization (MRO) algorithm is used select best among multiples. In addition, design (DTransL) boost accuracy targets. Davis, KIBA, Binding-DB examples benchmark datasets validate proposed model. Results exhibit MRO+DTransL outflanks existing cutting edge models. On Davis dataset, performed better than LSTM 9.742%, achieved an 98.398%. It reached 98.264% 97.344% on KIBA datasets, respectively, indicating improvements 8.608% 8.957% over baseline

Language: Английский

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Computational Discovery of Novel GPX4 Inhibitors from Herbal Sources as Potential Ferroptosis Inducers in Cancer Therapy

Archives of Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: unknown, P. 110231 - 110231

Published: Nov. 1, 2024

Language: Английский

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Mechanisms of ferroptotic and non-ferroptotic organ toxicity of chemotherapy: protective and therapeutic effects of ginger, 6-gingerol and zingerone in preclinical studies

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 5, 2024

Abstract Chemotherapy (CT) is one of the flagship options for treatment cancers worldwide. It involves use cytotoxic anticancer agents to kill or inhibit proliferation cancer cells. However, despite its clinical efficacy, CT triggers side effect toxicities in several organs, which may impact patient’s quality life and outcomes. While toxicity consistent with non-ferroptotic mechanisms involving oxidative stress, inflammation, mitochondrial impairment other aberrant signalling leading apoptosis necroptosis, recent studies show that ferroptosis, a non-apoptotic, iron-dependent cell death pathway, also involved pathophysiology organ toxicity. provokes ferroptosis via system Xc – /GPX-4/GSH/SLC7A11 axis depletion, ferritinophagy, iron overload, lipid peroxidation upregulation ferritin-related proteins. Cisplatin (CP) doxorubicin (DOX) are common drugs indicated induce vitro vivo. Studies have explored natural preventive therapeutic strategies using ginger rhizome major bioactive compounds, 6-gingerol (6G) zingerone (ZG), combat Ginger extract, 6G ZG mitigate dysfunction toxicity, but their effects on CT-induced remain unclear. Systematic investigations are, therefore, needed unfold roles ginger, as they potential prevention This review reveals ferroptotic protective against CT-induced, toxicities.

Language: Английский

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