ArticleScientific reports2014
Histone deacetylases inhibition by SAHA/Vorinostat normalizes the glioma microenvironment via xCT equilibration.
Article in Scientific reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- FSP1 and histone deacetylases suppress cancer persister cell ferroptosis.Science advances · 2026Article
- Acetylation modification in malignant progression and therapeutic resistance of gliomas.Frontiers in cell and developmental biology · 2026Review
- Mechanism by which SAHA regulates HLA-E expression via the endoplasmic reticulum stress-related PERK/ATF4/CHOP pathway in neuroblastoma.Frontiers in immunology · 2026Article
- The amino acid transporter SLC7A11 expression in breast cancer.Cancer biology & therapy · 2024Article
- Research Progress on the Mechanism of Histone Deacetylases in Ferroptosis of Glioma.Oncology reviews · 2024Review
- Metabolomic, DNA Methylomic, and Transcriptomic Profiling of Suberoylanilide Hydroxamic Acid Effects on LPS-Exposed Lung Epithelial Cells.Cancer prevention research (Philadelphia, Pa.) · 2023Article
- Ferroptosis and PPAR-gamma in the limelight of brain tumors and edema.Frontiers in oncology · 2023Review
- Investigational Microbiological Therapy for Glioma.Cancers · 2022Review
- Small-Molecule NSC59984 Induces Mutant p53 Degradation through a ROS-ERK2-MDM2 Axis in Cancer Cells.Molecular cancer research : MCR · 2022Article
- System XcInvestigational new drugs · 2021Review
- ING5-mediated antineuroblastoma effects of suberoylanilide hydroxamic acid.Cancer medicine · 2018Article
- A novel histone deacetylase inhibitor, CKD5, has potent anti-cancer effects in glioblastoma.Oncotarget · 2017Article
- SAHA and/or MG132 reverse the aggressive phenotypes of glioma cells: An in vitro and vivo study.Oncotarget · 2017Article
- Oxidative Stress Gene Expression Profile Correlates with Cancer Patient Poor Prognosis: Identification of Crucial Pathways Might Select Novel Therapeutic Approaches.Oxidative medicine and cellular longevity · 2017Review
- Epigenetics in Brain Tumors: HDACs Take Center Stage.Current neuropharmacology · 2016Review
- Opportunities and challenges of radiotherapy for treating cancer.Nature reviews. Clinical oncology · 2015Review
- Redox-Mediated Suberoylanilide Hydroxamic Acid Sensitivity in Breast Cancer.Antioxidants & redox signaling · 2015Article
- Neurodegeneration and the Brain Tumor Microenvironment. [corrected].Current neuropharmacology · 2015Article
- Glioblastoma cells induce differential glutamatergic gene expressions in human tumor-associated microglia/macrophages and monocyte-derived macrophages.Cancer biology & therapy · 2015Article
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Malignant gliomas are characterized by neurodegenerative actions leading to the destruction of surrounding brain parenchyma. The disturbance in glutamate homeostasis caused by increased expression of the glutamate transporter xCT plays a key role in glioma progression. We demonstrate that the HDAC-inhibitor SAHA specifically inhibits the xCT-transporter expression. Thereby, tumor cell stress is engendered, marked by increase in ROS. Moreover, SAHA dependent xCT-reduction correlates with the inhibition of ATF4-expression, a factor known to foster xCT expression. Since xCT/system Xc- is pivotal for the brain tumor microenvironment, normalization of this system is a key in the management of malignant gliomas. To date, the problem lay in the inability to specifically target xCT due to the ubiquitous expression of the xCT-transporter--i.e. in non-cancerously transformed cells too--as well as its essential role in physiological CNS processes. Here, we show xCT-transporter equilibration through SAHA is specific for malignant brain tumors whereas SAHA does not affect the physiological xCT levels in healthy brain parenchyma. Our data indicate that SAHA operates on gliomas specifically via normalizing xCT expression which in consequence leads to reduced extracellular glutamate levels. This in turn causes a marked reduction in neuronal cell death and normalized tumor microenvironment.
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