ArticleJournal of neurochemistry2009
Sulfasalazine inhibits the growth of primary brain tumors independent of nuclear factor-kappaB.
Article in Journal of neurochemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 83 citations in OpenAlex.
- LTF regulates glioblastoma progression and temozolomide resistance via the NF-κB signaling pathway.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2025Article
- Implication of system xJournal of neuroinflammation · 2024Article
- Effect of sulfasalazine on ferroptosis during intestinal injury in rats after liver transplantation.Scientific reports · 2024Article
- Immunotherapy against the Cystine/Glutamate Antiporter xCT Improves the Efficacy of APR-246 in Preclinical Breast Cancer Models.Biomedicines · 2022Article
- Chemical hybridization of sulfasalazine and dihydroartemisinin promotes brain tumor cell death.Scientific reports · 2021Article
- The multifaceted NF-kB: are there still prospects of its inhibition for clinical intervention in pediatric central nervous system tumors?Cellular and molecular life sciences : CMLS · 2021Review
- Inhibition of metabotropic glutamate receptor III facilitates sensitization to alkylating chemotherapeutics in glioblastoma.Cell death & disease · 2021Article
- Synergistic Effect of Perampanel and Temozolomide in Human Glioma Cell Lines.Journal of personalized medicine · 2021Article
- xCT: A Critical Molecule That Links Cancer Metabolism to Redox Signaling.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Review
- The XCellular oncology (Dordrecht, Netherlands) · 2020Article
- Erastin Inhibits Septic Shock and Inflammatory Gene Expression via Suppression of the NF-κB Pathway.Journal of clinical medicine · 2019Article
- Ferroptosis and Its Role in Diverse Brain Diseases.Molecular neurobiology · 2019Review
- Anti-Cancer Effects of Sulfasalazine and Vitamin E Succinate in MDA-MB 231 Triple-Negative Breast Cancer Cells.International journal of medical sciences · 2019Article
- Glutamate weighted imaging contrast in gliomas with 7 Tesla magnetic resonance imaging.NeuroImage. Clinical · 2019Article
- Perineuronal nets decrease membrane capacitance of peritumoral fast spiking interneurons in a model of epilepsy.Nature communications · 2018Article
- xCT (SLC7A11)-mediated metabolic reprogramming promotes non-small cell lung cancer progression.Oncogene · 2018Article
- Combination Therapy with Sulfasalazine and Valproic Acid Promotes Human Glioblastoma Cell Death Through Imbalance of the Intracellular Oxidative Response.Molecular neurobiology · 2018Article
- Glioma, glutamate (SLC7A11) and seizures-a commentary.Annals of translational medicine · 2017Article
- Behavioural Effects of Using Sulfasalazine to Inhibit Glutamate Released by Cancer Cells: A Novel target for Cancer-Induced Depression.Scientific reports · 2017Article
- Temozolomide toxicity operates in a xCT/SLC7a11 dependent manner and is fostered by ferroptosis.Oncotarget · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Nuclear factor-kappaB (NF-kappaB) is a pleiotropic transcription factor that generally enhances cellular resistance to apoptotic cell death. It has been shown to be constitutively active in some cancers and is being pursued as potential anticancer target. Sulfasalazine which is used clinically to treat Crohn's disease has emerged as a potential inhibitor of NF-kappaB and has shown promising results in two pre-clinical studies to target primary brain tumors, gliomas. Once digested, sulfasalazine is cleaved into sulfapyridine and 5-aminosalicylic acid (5-ASA; mesalamine) by colonic bacteria, and the latter, too, is reported to suppress NF-kappaB activity. We now show that glioma cells obtained from patient biopsies or glioma cell lines do not show significant constitutive NF-kappaB activation, unless exposed to inflammatory cytokines. This does not change when gliomas are implanted into the cerebrum of severe combined immun-deficient mice. Nevertheless, sulfasalazine but not its cleaved form 5-ASA caused a dose-dependent inhibition of glioma growth. This effect was entirely attributable to the inhibition of cystine uptake via the system x(c)(-) cystine-glutamate transporter. It could be mimicked by S-4-carboxy-phenylglycine (S-4-CPG) a more specific system x(c)(-) inhibitor, and lentiviral expression of a constitutively active form of IkappaB kinase b was unable to overcome the growth retarding effects of sulfasalazine or S-4-CPG. Both drugs inhibited cystine uptake causing a chronic depletion of intracellular GSH and consequently compromised cellular redox defense which stymied tumor growth. This data suggests that system x(c)(-) is a promising therapeutic target in gliomas and possibly other cancers and that it can be pharmacologically inhibited by Sulfasalazine, an FDA-approved drug.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.