ArticleThe Journal of biological chemistry2016
Multidrug Resistance-associated Protein-1 (MRP-1)-dependent Glutathione Disulfide (GSSG) Efflux as a Critical Survival Factor for Oxidant-enriched Tumorigenic Endothelial Cells.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04020419 (Natural Berry Extract Treatment of Hemangiomas), which is not on this map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Natural Berry Extract Treatment of Hemangiomas
Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
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- Maternal Thrombophilia Disrupts Fetal Redox Homeostasis.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Transcriptomic analysis of melatonin-mediated drought stress response genes in alfalfa during germination period.BMC plant biology · 2025Article
- Targeting ferroptosis opens new avenues for the development of novel therapeutics.Signal transduction and targeted therapy · 2023Review
- Glutathione-Mediated Neuroprotective Effect of Purine Derivatives.International journal of molecular sciences · 2023Review
- Tissue nanotransfection causes tumor regression by its effect on nanovesicle cargo that alters microenvironmental macrophage state.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Mesoporous nanodrug delivery system: a powerful tool for a new paradigm of remodeling of the tumor microenvironment.Journal of nanobiotechnology · 2023Review
- Mitochondria as Target for Tumor Management of Hemangioendothelioma.Antioxidants & redox signaling · 2021Article
- AITC induces MRP1 expression by protecting against CS/CSE-mediated DJ-1 protein degradationThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2020Article
- YB-1 transferred by gastric cancer exosomes promotes angiogenesis via enhancing the expression of angiogenic factors in vascular endothelial cells.BMC cancer · 2020Article
- Mitochondrial reactive oxygen species cause major oxidative mitochondrial DNA damages and repair pathways.Journal of biosciences · 2020Review
- Methylseleninic Acid Induces Lipid Peroxidation and Radiation Sensitivity in Head and Neck Cancer Cells.International journal of molecular sciences · 2019Article
- Glutathione reductase (American journal of cancer research · 2019Article
- Unraveling the Potential Role of Glutathione in Multiple Forms of Cell Death in Cancer Therapy.Oxidative medicine and cellular longevity · 2019Review
- Epidermal E-Cadherin Dependent β-Catenin Pathway Is Phytochemical Inducible and Accelerates Anagen Hair Cycling.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Phytochemical Inhibition of Multidrug Resistance Protein-1 as a Therapeutic Strategy for Hemangioendothelioma.Antioxidants & redox signaling · 2017Article
- Urinary Excretion of MicroRNA-126 Is a Biomarker for Hemangioma Proliferation.Plastic and reconstructive surgery · 2017Article
- Bixin and Fuxoxanthin Alone and in Combination with Cisplatin Regulate ABCC1 and ABCC2 Transcription in A549 Lung Cancer Cells.Journal of pharmacy & bioallied sciencesArticle
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Endothelial cell tumors are the most common soft tissue tumors in infants. Tumor-forming endothelial (EOMA) cells are able to escape cell death fate despite excessive nuclear oxidant burden. Our previous work recognized perinuclear Nox-4 as a key contributor to EOMA growth. The objective of this work was to characterize the mechanisms by which EOMA cells evade oxidant toxicity and thrive. In EOMA cells, compared with in the cytosol, the nuclear GSSG/GSH ratio was 5-fold higher. Compared to the ratio observed in healthy murine aortic endothelial (MAE) cells, GSSG/GSH was over twice as high in EOMA cells. Multidrug resistance-associated protein-1 (MRP-1), an active GSSG efflux mechanism, showed 2-fold increased activity in EOMA compared with MAE cells. Hyperactive YB-1 and Ape/Ref-1 were responsible for high MRP-1 expression in EOMA. Proximity ligand assay demonstrated MRP-1 and YB-1 binding. Such binding enabled the nuclear targeting of MRP-1 in EOMA in a leptomycin-B-sensitive manner. MRP-1 inhibition as well as knockdown trapped nuclear GSSG, causing cell death of EOMA. Disulfide loading of cells by inhibition of GSSG reductase (bischoloronitrosourea) or thioredoxin reductase (auranofin) was effective in causing EOMA death as well. In sum, EOMA cells survive a heavy oxidant burden by rapid efflux of GSSG, which is lethal if trapped within the cell. A hyperactive MRP-1 system for GSSG efflux acts as a critical survival factor for these cells, making it a potential target for EOMA therapeutics.
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