Ibuprofen induces ferroptosis of glioblastoma cells via downregulation of nuclear factor erythroid 2-related factor 2 signaling pathway

In this study, we first found that ibuprofen inhibited the viabilities of glioblastoma cells in vitro and in vivo, accompanied by abnormal increase in intracellular lipid peroxidation. Further study showed that the cell growth inhibition caused by ibuprofen could be rescued by the ferroptosis inhibitors deferoxamine (DFO), ferrostatin-1 and Liproxstatin-1. Nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) are key regulators of ferroptosis. Our data showed that Nrf2, GPX4 and SLC7A11 were downregulated in glioblastoma cells under ibuprofen treatment. Interestingly, we found that decreased mRNA expression of GPX4 and SLC7A11 was accompanied with reduced Nrf2, which is a redox sensitive transcription factor that controls the expression of intracellular redox-balancing proteins such as GPX4 and SLC7A11. All the data suggested that Nrf2 could regulate the expression of GPX4 and SLC7A11 in glioma cells. Taken together, our findings reveal that ibuprofen could induce ferroptosis of glioblastoma cells via downregulation of Nrf2 signaling pathway and is a potential drug for glioma treatment.
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

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This study aimed to determine the main single nucleotide polymorphisms that are associated with an increased or decreased risk of glioma development in healthy individuals. We conducted a systematic review of the articles published in English on the PUBMED database between January 2008 and December 2017. Our search resulted in a total of 743 articles; however, only 56 were included in this review. A total of 148 polymorphisms were found, which involved 64 different genes. The polymorphisms that were most associated with an increased risk of glioma development were polymorphic variants rs179782, rs13181, and rs3791679 of th...
Source: Cancer Investigation - Category: Cancer & Oncology Tags: Cancer Invest Source Type: research
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Source: Trends in Pharmacological Sciences - Category: Drugs & Pharmacology Source Type: research
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Source: Acta Neuropathologica - Category: Neurology Source Type: research
AbstractThe neurotrophin receptor tyrosine kinase (NTRK1-3) genes have been identified as key fusion partners in a range of pediatric cancers. In childhood cancers,ETV6-NTRK3 fusions are found in the majority of infantile fibrosarcomas and congenital mesoblastic nephromas.NTRK fusions are also found in mammary analog secretory carcinomas (MASC), secretory breast carcinomas, and with modest frequency in high-grade gliomas in very young children. While there are a range of multi-receptor tyrosine kinase inhibitors that show efficacy against TRK kinases, there are now multiple highly selective TRK inhibitors in clinical evalu...
Source: Pediatric Drugs - Category: Pediatrics Source Type: research
Neuropilin-2 (NRP2) is a prognostic indicator for reduced survival in bladder cancer (BCa) patients. Together with its major ligand, vascular endothelial growth factor (VEGF)-C, NRP2 expression is a predictive factor for treatment outcome in response to radiochemotherapy in BCa patients who underwent transurethral resection. Therefore, we investigated the benefit of combining cisplatin-based chemotherapy with irradiation treatment in the BCa cell line RT112 exhibiting or lacking endogenous NRP2 expression in order to evaluate NRP2 as potential therapeutic target. We have identified a high correlation of NRP2 and the glioma...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
ConclusionAs a new anticancer drug, whether itraconazole eventually entering clinical application requires the joint eforts of all scholars. In any case, an in-depth study on itraconazole will bring new hope for cancer patients in the near future.
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research
Abstract Glioma is the most common type of primary brain tumor, and it has a high mortality rate. Currently, there are only a few therapeutic approaches for gliomas, and their effects are unsatisfactory. Therefore, uncovering the pathogenesis and exploring more therapeutic strategies for the treatment of gliomas are urgently needed to overcome the ongoing challenges. Cellular redox imbalance has been shown to be associated with the initiation and progression of gliomas. Among reactive oxygen species (ROS), hydrogen peroxide (H2O2) is considered the most suitable for redox signaling and is a potential candidate as ...
Source: Archives of Pharmacal Research - Category: Drugs & Pharmacology Authors: Tags: Arch Pharm Res Source Type: research
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Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Introduction: The body of glioma-related literature has grown significantly over the past 25 years. Despite this growth in the amount of published research, gliomas remain one of the most intransigent cancers. The purpose of this study was to analyze the landscape of glioma-related research over the past 25 years using machine learning and text analysis.Methods: In April 2019, we downloaded glioma-related publications indexed in PubMed between 1994 and 2018. We used Python to extract the title, publication date, MeSH terms, and abstract from the metadata of each publication for bibliometric assessment. Latent Dirichlet all...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Authors: Xu R, Zhou F, Yu T, Xu G, Zhang J, Wang Y, Zhao L, Liu N Abstract MicroRNAs have been found ectopically expressed in many cancers and play essential roles in tumor EMT progress. Recent studies identified decreased miR-940 expression in glioma cells and may serve as a tumor-suppressor. However, whether miR-940 involve in glioma EMT remain poorly understood. Here we confirmed that miR-940 was significantly reduced in glioma cells and tissues. Introduction of miR-940 dramatically suppressed invasion and migration of glioma cells. Gain-of-function experiments showed ZEB2 as a direct target of miR-940, knockdow...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
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