ArticleJournal of experimental & clinical cancer research : CR2010
Effects of valproic acid on the cell cycle and apoptosis through acetylation of histone and tubulin in a scirrhous gastric cancer cell line.
Article in Journal of experimental & clinical cancer research : CR, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 53 citations in OpenAlex.
- Paclitaxel plus valproic acid versus paclitaxel alone as second- or third-line therapy for advanced gastric cancer: a randomized Phase II trial.Drug design, development and therapy · 2016Trial
- EPAS1 increases SDHA to inhibit proliferation of multiple myeloma cells by restoring TCA Cycle.NPJ precision oncology · 2025Article
- Valproic Acid Enhances the Anticancer Effect of L-Ascorbic Acid by Upregulating Sodium-Dependent Vitamin C Transporter 2 in Colorectal Cancer.Antioxidants (Basel, Switzerland) · 2025Article
- A New Treatment Strategy for Lung Cancer With HDAC and Wnt/β-Catenin Pathway Inhibitors.IUBMB life · 2025Article
- Exploring potential biomarkers and lead molecules in gastric cancer by network biology, drug repurposing and virtual screening strategies.Molecular diversity · 2025Article
- Mechanistic Insights about Sorafenib-, Valproic Acid- and Metformin-Induced Cell Death in Hepatocellular Carcinoma.International journal of molecular sciences · 2024Review
- HDAC2 as a target for developing anti-cancer drugs.Computational and structural biotechnology journal · 2023Review
- Repurposed Drugs in Gastric Cancer.Molecules (Basel, Switzerland) · 2022Review
- Article
- Anticancer Effects of Valproic Acid via Regulation of Epigenetic Mechanisms in Non-small-cell Lung Cancer A549 Cell Line.Iranian journal of pharmaceutical research : IJPR · 2021Article
- Serum-Free Medium for Recombinant Protein Expression in Chinese Hamster Ovary Cells.Frontiers in bioengineering and biotechnology · 2021Review
- Embryo-derived teratoma in vitro biological system reveals antitumor and embryotoxic activity of valproate.The FEBS journal · 2020Article
- Refocusing the Use of Psychiatric Drugs for Treatment of Gastrointestinal Cancers.Frontiers in oncology · 2020Review
- G protein-coupled receptor kinase 5 modifies cancer cell resistance to paclitaxel.Molecular and cellular biochemistry · 2019Article
- N-acetylcysteine decreases malignant characteristics of glioblastoma cells by inhibiting Notch2 signaling.Journal of experimental & clinical cancer research : CR · 2019Article
- Synergistic induction of apoptosis in a cell model of human leukemia K562 by nitroglycerine and valproic acid.EXCLI journal · 2019Article
- Histone Deacetylase Inhibitor Modulates NKG2D Receptor Expression and Memory Phenotype of Human Gamma/Delta T Cells Upon Interaction With Tumor Cells.Frontiers in immunology · 2019Article
- Valproic acid treatment response in vitro is determined by TP53 status in medulloblastoma.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2018Article
- Therapeutic positioning of secretory acetylated APE1/Ref-1 requirement for suppression of tumor growth in triple-negative breast cancer in vivo.Scientific reports · 2018Article
- Low-dose valproic acid with low-dose gemcitabine augments MHC class I-related chain A/B expression without inducing the release of soluble MHC class I-related chain A/B.Oncology letters · 2017Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundManagement of peritoneal dissemination is the most critical problem in gastric cancer. This study was performed to investigate the inhibitory effects of valproic acid (VPA) on a highly peritoneal-seeding cell line of human scirrhous gastric cancer, OCUM-2MD3, and to explore the mechanism and the potential of VPA.
methodsThe effects of VPA on the growth of OCUM-2MD3 cells were assessed by MTT assay. In addition, paclitaxel (PTX) was combined with VPA to evaluate their synergistic effects. HDAC1 and HDAC2 expression were evaluated by western blotting in OCUM-2MD3 cells and other gastric cancer cell lines (TMK-1, MKN-28). The acetylation status of histone H3 and α-tubulin after exposure to VPA were analyzed by western blotting. The activities of cell cycle regulatory proteins and apoptosis-modulating proteins were also examined by western blotting. The effects of VPA in vivo were evaluated in a xenograft model, and apoptotic activity was assessed by TUNEL assay.
resultsOCUM-2MD3 cells showed high levels of HDAC1 and HDAC2 expression compared with TMK-1 and MKN-28. The concentration of VPA required for significant inhibition of cell viability (P < 0.05) was 5 mM at 24 h and 0.5 mM at 48 h and 72 h. The inhibition of VPA with PTX showed dose-dependent and combinatorial effects. VPA increased acetyl-histone H3, acetyl-α-tubulin, and p21WAF1 levels accompanied by upregulation of p27, caspase 3, and caspase 9, and downregulation of bcl-2, cyclin D1, and survivin. In the xenograft model experiment, the mean tumor volume of the VPA-treated group was significantly reduced by 36.4%, compared with that of the control group at 4 weeks after treatment (P < 0.01). The apoptotic index was significantly higher in the VPA-treated group (42.3% ± 3.5%) than in the control group (7.7% ± 2.5%) (P < 0.001).
conclusionsVPA induced dynamic modulation of histone H3 and α-tubulin acetylation in relation with the anticancer effect and the enhancement of PTX in the OCUM-2MD3 cell line. Therefore, VPA in combination with PTX is expected to be a promising therapy for peritoneal dissemination of scirrhous gastric cancer.
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