ArticleThe Journal of biological chemistry2016
Induction of Glycosphingolipid GM3 Expression by Valproic Acid Suppresses Cancer Cell Growth.
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. Cited by 17 papers.
What it found
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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.
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Who cites it
17 citing papers in PubMed, 39 citations in OpenAlex.
- Valproic acid as adjuvant treatment for convulsive status epilepticus: a randomised clinical trial.Critical care (London, England) · 2023Trial
- From molecular mechanisms of glycosphingolipid function to bio-therapeutic applications.Cellular and molecular life sciences : CMLS · 2026Review
- Ganglioside GM3 in the Tumor Microenvironment: Mechanisms of Signaling Regulation and Strategies for Angiogenesis Inhibition.Biomolecules · 2026Review
- Gangliosides in molecular interactions and cell regulation.The Journal of biological chemistry · 2026Review
- St3gal5-mediated sialylation of glyco-CD177 on neutrophils restricts neuroinflammation following CNS injury.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Repurposing of nervous system drugs for cancer treatment: recent advances, challenges, and future perspectives.Discover oncology · 2025Review
- Enhanced Levels of Glycosphingolipid GM3 Delay the Progression of Diabetic Nephropathy.International journal of molecular sciences · 2023Article
- Glycosphingolipid GM3 prevents albuminuria and podocytopathy induced by anti-nephrin antibody.Scientific reports · 2022Article
- Article
- DNA damage response in vascular endothelial senescence: Implication for radiation-induced cardiovascular diseases.Journal of radiation research · 2021Review
- Gangliosides as Signaling Regulators in Cancer.International journal of molecular sciences · 2021Review
- Inhibition of Ganglioside Synthesis Suppressed Liver Cancer Cell Proliferation through Targeting Kinetochore Metaphase Signaling.Metabolites · 2021Article
- Valproic Acid: A Promising Therapeutic Agent in Glioma Treatment.Frontiers in oncology · 2021Review
- Article
- Downregulation of ST3GAL5 is associated with muscle invasion, high grade and a poor prognosis in patients with bladder cancer.Oncology letters · 2020Article
- Epigenetics and Sphingolipid Metabolism in Health and Disease.International journal of biopharmaceutical sciences · 2018Article
- Distinctive epigenomes characterize glioma stem cells and their response to differentiation cues.Genome biology · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glycosphingolipid GM3, a known suppressor of epidermal growth factor receptor (EGFR) phosphorylation, inhibits cell proliferation. Valproic acid, conversely, is known as an up-regulator of GM3 synthase gene (ST3GAL5). To test the possibility that valproic acid could inhibit EGFR phosphorylation by increasing the level of GM3 in cells, we treated A431 epidermoid carcinoma cells with valproic acid and found that valproic acid treatment caused an about 6-fold increase in the GM3 level but only a marginal increase in the GM2 level in these cells and that the observed increase in GM3 level was valproic acid dose-dependent. Consistent with this observation, valproic acid treatment induced GM3 synthase gene expression by about 8-fold. Furthermore, phosphorylation of EGFR was reduced, and cell proliferation was inhibited following valproic acid treatment. Consistent with these results, transient expression of GM3 synthase gene in A431 cells also increased cellular level of GM3, reduced phosphorylation of EGFR, and inhibited cell proliferation. Treatment with l-phenyl-2-decanoylamino-3-morpholino-l-propanol, an inhibitor of glucosylceramide synthesis, decreased the cellular level of GM3 and reduced the inhibitory effects of valproic acid on EGFR phosphorylation and cell proliferation. These results suggested that induction of GM3 synthesis was enough to inhibit proliferation of cancer cells by suppressing EGFR activity. Valproic acid treatment similarly increased the GM3 level and reduced phosphorylation of EGFR in U87MG glioma cells and inhibited their proliferation. These results suggested that up-regulators of GM3 synthase gene, such as valproic acid, are potential suppressors of cancer cell proliferation.
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What OpenQuestion holds
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.