ArticleCellular oncology (Dordrecht, Netherlands)2014
Deoxyhypusine synthase (DHPS) inhibitor GC7 induces p21/Rb-mediated inhibition of tumor cell growth and DHPS expression correlates with poor prognosis in neuroblastoma patients.
Article in Cellular oncology (Dordrecht, Netherlands), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Development and validation of an immune-related diagnostic signature for breast cancer bone metastasis.Scientific reports · 2026Article
- Polyamine Metabolism and the DHPS/eIF5A Hypusination Axis: From Metabolic Reprogramming to a Therapeutic Achilles' Heel in Melanoma.Biomolecules · 2026Review
- Epithelial hypusination regulates Helicobacter pylori-induced gastric inflammation.Amino acids · 2026Article
- Epithelial Hypusination Regulates Helicobacter pylori-induced Gastric Inflammation.Research square · 2025Article
- Polyamine Inhibition with DFMO: Shifting the Paradigm in Neuroblastoma Therapy.Journal of clinical medicine · 2025Review
- Hypusinated and unhypusinated isoforms of the translation factor eIF5A exert distinct effects in models of pancreas development and function.The Journal of biological chemistry · 2025Article
- Overcoming resistance to arginine deprivation therapy using GC7 in pleural mesothelioma.iScience · 2025Article
- Knockout or inhibition of DHPS suppresses ovarian tumor growth and metastasis by attenuating the TGFβ pathway.Scientific reports · 2025Article
- A multispectral 3D live organoid imaging platform to screen probes for fluorescence guided surgery.EMBO molecular medicine · 2024Article
- Unsaturated Fatty Acid Synthesis Is Associated with Worse Survival and Is Differentially Regulated byCancers · 2024Article
- Inhibiting eukaryotic initiation factor 5A (eIF5A) hypusination attenuated activation of the SIK2 (salt-inducible kinase 2)-p4E-BP1 pathway involved in ovarian cancer cell proliferation and migration.Molecular biology reports · 2023Article
- New K50R mutant mouse models reveal impaired hypusination of eif5a2 with alterations in cell metabolite landscape.Biology open · 2023Article
- Role of eIF5A in Mitochondrial Function.International journal of molecular sciences · 2022Review
- eIF5A-Independent Role of DHPS in p21International journal of molecular sciences · 2021Article
- Catastrophic ATP loss underlies a metabolic combination therapy tailored forProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Proteomic Analysis on Anti-Proliferative and Apoptosis Effects of Curcumin Analog, 1,5-bis(4-Hydroxy-3-Methyoxyphenyl)-1,4-Pentadiene-3-One-Treated Human Glioblastoma and Neuroblastoma Cells.Frontiers in molecular biosciences · 2021Article
- Blockade of EIF5A hypusination limits colorectal cancer growth by inhibiting MYC elongation.Cell death & disease · 2020Article
- Eukaryotic translation initiation factor 5A in the pathogenesis of cancers.Oncology letters · 2020Review
- Polyamine synthesis as a target ofThe Journal of biological chemistry · 2018Review
- Eukaryotic translation initiation factor 5A-2 involves in doxorubicin-induced epithelial-mesenchymal transition in oral squamous cell carcinoma cells.Journal of Cancer · 2018Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeNeuroblastoma (NB) is an aggressive pediatric malignancy that typically occurs in infants and children under the age of 5 years. High-stage tumors relapse frequently even after aggressive multimodal treatment, resulting in therapy resistance and eventually in patient death. Clearly, new biologically-targeted drugs are needed that more efficiently suppress tumor growth and prevent relapse. We and others previously showed that polyamines such as spermidine play an essential role in NB tumorigenesis and that DFMO, an inhibitor of the central polyamine synthesis gene ODC, is effective in vitro and in vivo, prompting its evaluation in NB clinical trials. However, the specific molecular actions of polyamines remain poorly defined. Spermidine and deoxyhypusine synthase (DHPS) are essential components in the hypusination-driven post-translational activation of eukaryotic initiation factor 5A (eIF5A).
methodsWe assessed the role of DHPS in NB and the impact of its inhibition by N(1)-guanyl-1,7-diaminoheptane (GC7) on tumor cell growth using cell proliferation assays, Western blot, immunofluorescence microscopy, and Affymetrix micro-array mRNA expression analyses in NB tumor samples.
resultsWe found that GC7 inhibits NB cell proliferation in a dose-dependent manner, through induction of the cell cycle inhibitor p21 and reduction of total and phosphorylated Rb proteins. Strikingly, high DHPS mRNA expression correlated significantly with unfavorable clinical parameters, including poor patient survival, in a cohort of 88 NB tumors (all P < 0.04).
conclusionsThese results suggest that spermidine and DHPS are key contributing factors in NB tumor proliferation through regulation of the p21/Rb signaling axis.
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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.