ArticleScientific reports2015
XI-006 induces potent p53-independent apoptosis in Ewing sarcoma.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Side-stepping the guardian of the genome: current cancer therapeutics targeting mutant p53.Frontiers in pharmacology · 2025Review
- Integrated drug response prediction models pinpoint repurposed drugs with effectiveness against rhabdomyosarcoma.PloS one · 2024Article
- MDMX in Cancer: A Partner of p53 and a p53-Independent Effector.Biologics : targets & therapy · 2024Review
- Identification of G-protein signaling modulator 2 as a diagnostic and prognostic biomarker of pancreatic adenocarcinoma: an exploration of its regulatory mechanisms.Journal of gastrointestinal oncology · 2021Article
- The roles and regulation of MDM2 and MDMX: it is not just about p53.Genes & development · 2021Review
- MDM4 inhibition: a novel therapeutic strategy to reactivate p53 in hepatoblastoma.Scientific reports · 2021Observational
- Recent Synthetic Approaches towards Small Molecule Reactivators of p53.Biomolecules · 2020Review
- MDM2 and MDMX promote ferroptosis by PPARα-mediated lipid remodeling.Genes & development · 2020Article
- Targeting MDMX for Cancer Therapy: Rationale, Strategies, and Challenges.Frontiers in oncology · 2020Review
- Anti-Cancer Activity of Novel Dihydrotestosterone-Derived Ring A-Condensed Pyrazoles on Androgen Non-Responsive Prostate Cancer Cell Lines.International journal of molecular sciences · 2019Article
- Genome-scale CRISPR-Cas9 screen identifies druggable dependencies inThe Journal of experimental medicine · 2018Article
- Activation of p53 and destabilization of androgen receptor by combinatorial inhibition of MDM2 and MDMX in prostate cancer cells.Oncotarget · 2018Article
- Reviving the guardian of the genome: Small molecule activators of p53.Pharmacology & therapeutics · 2017Review
- Mutant p53 upregulates alpha-1 antitrypsin expression and promotes invasion in lung cancer.Oncogene · 2017Article
- Silver nanoparticles defeat p53-positive and p53-negative osteosarcoma cells by triggering mitochondrial stress and apoptosis.Scientific reports · 2016Article
- Article
- Vorinostat Enhances Cytotoxicity of SN-38 and Temozolomide in Ewing Sarcoma Cells and Activates STAT3/AKT/MAPK Pathways.PloS one · 2015Article
- GPSM2 Serves as an Independent Prognostic Biomarker for Liver Cancer Survival.Technology in cancer research & treatmentArticle
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is an imperious need for the development of novel therapeutics for the treatment of Ewing sarcoma, the second most prevalent solid bone tumour observed in children and young adolescents. Recently, a 4-nitrobenzofuroxan derivative, XI-006 (NSC207895) was shown to diminish MDM4 promoter activity in breast cancer cell lines. As amplification of MDM4 is frequently observed in sarcomas, this study examined the therapeutic potential of XI-006 for the treatment of Ewing and osteosarcoma. XI-006 treatment of Ewing and osteosarcoma cell lines (n = 11) resulted in rapid and potent apoptosis at low micro-molar concentrations specifically in Ewing sarcoma cell lines (48 hr IC50 0.099-1.61 μM). Unexpectedly, apoptotic response was not dependent on MDM4 mRNA/protein levels or TP53 status. Alkaline/neutral comet and γH2AX immunofluorescence assays revealed that the cytotoxic effects of XI-006 could not be attributed to the induction of DNA damage. RNA expression analysis revealed that the mechanism of action of XI-006 could be accredited to the inhibition of cell division and cycle regulators such as KIF20A and GPSM2. Finally, potent synergy between XI-006 and olaparib (PARP inhibitor) were observed due to the down-regulation of Mre11. Our findings suggest that XI-006 represents a novel therapeutic intervention for the treatment of Ewing sarcoma.
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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.