Computational and Theoretical Chemistry, Год журнала: 2024, Номер unknown, С. 114997 - 114997
Опубликована: Ноя. 1, 2024
Язык: Английский
ACS Omega, Год журнала: 2024, Номер 9(14), С. 16676 - 16686
Опубликована: Апрель 1, 2024
Oxaliplatin (Oxa) is a commonly used chemotherapy drug in the treatment of gastric cancer, but its toxic side effects and resistance after long-term use have seriously limited efficacy. Loading drugs with nanomaterials delivering them to tumor site are common ways overcome above problems. However, as carriers do not therapeutic functions on their own, effect single relatively limited, so there still room for progress related research. Herein, we construct Oxa@Mil-100(Fe) nanocomposites by loading Oxa metal–organic framework (MOF) Mil-100(Fe) high biocompatibility large specific surface area. The pore structure conducive amount drug-loading rate up 27.2%. responsive microenvironment (TME) can release Fe3+ under external stimulation. On one hand, inhibit synthesis DNA induce apoptosis cancer cells. other clear overexpressed glutathione (GSH) TME be reduced Fe2+, inhibiting activity peroxidase 4 (GPX4), leading accumulation intracellular lipid peroxides (LPO), at same time releasing number reactive oxygen species (ROS) through Fenton reaction, inducing ferroptosis With combination ferroptosis, shows good effect, killing cells obvious. In nude mouse model subcutaneous transplantation, significant inhibitory growth, an inhibition nearly 60%. addition excellent antitumor activity, has no obvious or effects. This study provides new idea method combined cancer.
Язык: Английский
Процитировано
9
Communications Biology, Год журнала: 2024, Номер 7(1)
Опубликована: Апрель 2, 2024
Abstract The occurrence of chemoresistance is an inescapable obstacle affecting the clinical efficacy cisplatin in gastric cancer (GC). Exploring regulatory mechanism resistance will help to provide potential effective targets for improving prognosis patients. Here, we find that FAM120A upregulated GC tissues and higher cisplatin-resistant tissues, its high expression positively correlated with poor outcome Functional studies indicate confers cells by inhibiting ferroptosis. Mechanically, METTL3-induced m6A modification YTHDC1-induced stability mRNA enhance expression. inhibits ferroptosis binding SLC7A11 enhancing stability. deficiency enhances sensitivity promoting vivo. These results reveal function chemotherapy tolerance targeting strategy alleviate GC.
Язык: Английский
Процитировано
7
Translational Gastroenterology and Hepatology, Год журнала: 2025, Номер 10, С. 7 - 7
Опубликована: Янв. 1, 2025
Gastrointestinal adenocarcinomas (GIACs) are common malignant tumors with poor prognosis in the world. Ferroptosis, characterized by accumulation of intracellular iron and lipid reactive oxygen species, emerges as a pivotal process tumorigenesis cancer advancement. However, implications ferroptosis-related genes GIAC remain to be elucidated. This study aimed at exploring potential role on treatment GIAC. In our study, comprehensive clinical, transcriptomic, and/or genomic data were acquired from The Cancer Genome Atlas (TCGA), Cell Line Encyclopedia (CCLE), Genomics Drug Sensitivity (GDSC), Gene Expression Omnibus (GEO). We formulated ferroptosis-score within TCGA cohort through gene set variation analysis (GSVA) subsequently validated 4 GEO datasets (GSE84437, GSE17536, GSE103479, GSE19417). sensitivity immunotherapy efficacy analyzed GDSC dataset PRJEB25780 cohort, respectively. was significantly associated favorable overall survival both training [TCGA: P=0.003; hazard ratio (HR), 0.67, 95% confidence interval (95% CI): 0.52-0.87] across four validation cohorts (GSE17536: P=0.03; HR, 0.57, CI: 0.34-0.96; GSE19417: P=0.047; 0.53, 0.28-1.01; GSE84437: P=0.004; 0.68, 0.51-0.90; GSE103479: 0.55, 0.32-0.96). Furthermore, correlated activation DNA damage repair pathway resistance cisplatin. Notably, GIACs low ferroptosis-scores exhibited heightened expression immune checkpoint molecules such programmed death-(ligand) 1 cytotoxic T lymphocyte antigen-4, elevated densities tumor-infiltrating CD8+ cells, response pembrolizumab monotherapy. Our findings delineated clinical relevance demonstrated utility predicting effectiveness.
Язык: Английский
Процитировано
0
Molecular and Cellular Probes, Год журнала: 2025, Номер 79, С. 102013 - 102013
Опубликована: Янв. 24, 2025
Язык: Английский
Процитировано
0
Journal of Medicinal Chemistry, Год журнала: 2025, Номер 68(3), С. 3309 - 3323
Опубликована: Янв. 30, 2025
A highly selective ferroptosis inducer with drug-like properties can significantly advance the research on inducing for anticancer treatment. We previously reported a active GPX4 inhibitor 26a, but its activity and stability need further improvement. In this work, novel (R)-9i more potent cytotoxicity (IC50 = 0.0003 μM against HT1080) selectivity (selectivity index 24933) was gained via electrophilic warhead screening structure-based optimization. The cellular thermal shift assay (CETSA) indicated that could stabilize Tm value of 6.2 °C. Furthermore, showed strong binding affinity (KD 20.4 nM). More importantly, has favorable pharmacokinetic than which endowed potential in antitumor as tool drug study ferroptosis. Associated these, treatment inhibited tumor growth xenograft mouse model without detectable toxicity.
Язык: Английский
Процитировано
0
iScience, Год журнала: 2025, Номер 28(3), С. 111964 - 111964
Опубликована: Фев. 7, 2025
Gastric cancer (GC) is one of the most prevalent and lethal cancers worldwide. Ferroptosis a form iron-dependent regulated cell death emerging as promising strategy for therapy, whereas regulation mechanism remains unclear. WTX has been recognized potential tumor suppressor, but attempts at targeted therapy have not achieved substantial progress. Further research into structure, function, mechanisms urgently needed. Herein, we identified long isoform (WTX-L) potent ferroptosis effector in GC. Mechanistically, WTX-L competitively interacts with β-arrestin2, disrupting its direct binding to IκBα subsequently activating NF-κB/LCN2 pathway. LCN2 further triggers by significantly increasing labile Fe2+ pool promoting excessive lipid peroxidation. Blockade WTX-L/β-arrestin2/NF-κB/LCN2 axis diminished activity inducers (erastin RSL3) vivo. Collectively, these findings reveal that targeting vulnerabilities through may represent
Язык: Английский
Процитировано
0
Medical Oncology, Год журнала: 2025, Номер 42(4)
Опубликована: Март 6, 2025
Язык: Английский
Процитировано
0
Phytomedicine, Год журнала: 2025, Номер unknown, С. 156789 - 156789
Опубликована: Апрель 1, 2025
Язык: Английский
Процитировано
0
Cancer Letters, Год журнала: 2024, Номер 591, С. 216857 - 216857
Опубликована: Апрель 5, 2024
Язык: Английский
Процитировано
3
Redox Biology, Год журнала: 2024, Номер 76, С. 103328 - 103328
Опубликована: Авг. 26, 2024
Over the past 30 years, survival rate for osteosarcoma (OS) has remained stagnant, indicating persistent challenges in diagnosis and treatment. Photodynamic therapy (PDT) emerged as a novel promising treatment modality OS. Despite apoptosis being primary mechanism attributed to PDT, it fails overcome issues such low efficacy resistance. Ferroptosis, Fe2+-dependent cell death process, potential enhance PDT's by increasing reactive oxygen species (ROS) through Fenton reaction. In this study, we investigated anti-tumor of PDT introduced an innovative therapeutic strategy that synergistically induces ferroptosis. Furthermore, have identified HERC1 pivotal protein involved ubiquitination degradation NCOA4, while also uncovering regulatory factor involving NRF2. Ultimately, targeting HERC1-NCOA4 axis during successfully achieved full activation ferroptosis, which significantly enhanced PDT. conclusion, these findings provide new theoretical evidence further characterizing offer molecular targets
Язык: Английский
Процитировано
2