ArticleJournal of cancer research and clinical oncology2016
Valproic acid (VPA) inhibits the epithelial-mesenchymal transition in prostate carcinoma via the dual suppression of SMAD4.
Article in Journal of cancer research and clinical oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Current research of the Notch pathway in hepatocellular carcinoma.European journal of medical research · 2025Review
- Ubiquitination Process Mediates Prostate Cancer Development and Metastasis through Multiple Mechanisms.Cell biochemistry and biophysics · 2024Review
- The role of short-chain fatty acid metabolism in the pathogenesis, diagnosis and treatment of cancer.Frontiers in oncology · 2024Review
- From HDAC to Voltage-Gated Ion Channels: What's Next? The Long Road of Antiepileptic Drugs Repositioning in Cancer.Cancers · 2022Review
- Regulation of epithelial-mesenchymal transition by protein lysine acetylation.Cell communication and signaling : CCS · 2022Review
- SMAD4 contributes to chondrocyte and osteocyte development.Journal of cellular and molecular medicine · 2022Review
- Valproic Acid Inhibits Glioma and Its Mechanisms.Journal of healthcare engineering · 2022Article
- Evaluation of the Effects of Valproic Acid Treatment on Cell Survival and Epithelial-Mesenchymal Transition-Related Features of Human Gastric Cancer Cells.Journal of gastrointestinal cancer · 2021Article
- Article
- Vimentin as a target for the treatment of COVID-19.BMJ open respiratory research · 2020Article
- Tackle Epithelial-Mesenchymal Transition With Epigenetic Drugs in Cancer.Frontiers in pharmacology · 2020Review
- Histone deacetylase inhibitors promote epithelial-mesenchymal transition in Hepatocellular CarcinomaTheranostics · 2020Article
- Review
- Glyoxalase 1 sustains the metastatic phenotype of prostate cancer cells via EMT control.Journal of cellular and molecular medicine · 2018Article
- Valproic acid sensitizes metformin-resistant human renal cell carcinoma cells by upregulating H3 acetylation and EMT reversal.BMC cancer · 2018Article
- Article
- The EMT spectrum and therapeutic opportunities.Molecular oncology · 2017Review
- Combination of sorafenib and Valproic acid synergistically induces cell apoptosis and inhibits hepatocellular carcinoma growth via down-regulating Notch3 and pAkt.American journal of cancer research · 2017Article
- MiR-130a-3p regulates cell migration and invasion via inhibition of Smad4 in gemcitabine resistant hepatoma cells.Journal of experimental & clinical cancer research : CR · 2016Article
- Epigenetic modulators as therapeutic targets in prostate cancer.Clinical epigenetics · 2016Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposesThe epithelial-mesenchymal transition (EMT) plays an important role in cancer metastasis. Previous studies have reported that valproic acid (VPA) suppresses prostate carcinoma (PCa) cell metastasis and down-regulates SMAD4 protein levels, which is the key molecule in TGF-β-induced EMT. However, the correlation between VPA and the EMT in PCa remains uncertain.
methodsMarkers of the EMT in PCa cells and xenografts were molecularly assessed after VPA treatment. The expression and mono-ubiquitination of SMAD4 were also analyzed. After transfection with plasmids that express SMAD4 or short hairpin RNA for SMAD4 down-regulation, markers of EMT were examined to confirm whether VPA inhibits the EMT of PCa cells through the suppression of SMAD4.
resultsVPA induced the increase in E-cadherin (p < 0.05), and the decrease in N-cadherin (p < 0.05) and Vimentin (p < 0.05), in PCa cells and xenografts. SMAD4 mRNA and protein levels were repressed by VPA (p < 0.05), whereas the level of mono-ubiquitinated SMAD4 was increased (p < 0.05). SMAD4 knockdown significantly increased E-cadherin expression in PC3 cells, but SMAD4 over-expression abolished the VPA-mediated EMT-inhibitory effect.
conclusionsVPA inhibits the EMT in PCa cells via the inhibition of SMAD4 expression and the mono-ubiquitination of SMAD4. VPA could serve as a promising agent in PCa treatment, with new strategies based on its diverse effects on posttranscriptional regulation.
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