ArticleThe Journal of biological chemistry2010
Histone deacetylase inhibitor valproic acid inhibits cancer cell proliferation via down-regulation of the alzheimer amyloid precursor protein.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 citations in OpenAlex.
- Gut Microbiota Dysbiosis and Neuroinflammation in Alzheimer's Disease: a Systematic Review of Mechanistic Insights.Molecular neurobiology · 2026Pooled it
- Beyond epilepsy: The expanding role of valproic acid in Alzheimer disease therapy - a review.The Journal of pharmacology and experimental therapeutics · 2025Review
- Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook.Frontiers in genetics · 2025Review
- Neuroprotective Strategies and Cell-Based Biomarkers for Manganese-Induced Toxicity in Human Neuroblastoma (SH-SY5Y) Cells.Biomolecules · 2024Article
- Repurposed Drugs in Gastric Cancer.Molecules (Basel, Switzerland) · 2022Review
- Effects of Luteolin on Human Breast Cancer Using Gene Expression Array: Inferring Novel Genes.Current issues in molecular biology · 2022Article
- Article
- Histone deacetylase inhibitors as a novel therapeutic approach for pheochromocytomas and paragangliomas.Oncology research · 2022Review
- Genome-Wide Analysis of microRNA and mRNA Expression in Colorectal Intramucosal Neoplasia and Colorectal Cancer With a Microsatellite-Stable Phenotype Based on Adenoma-Carcinoma Sequences.Frontiers in oncology · 2022Article
- Combined evaluation of proliferation and apoptosis to calculate ICMedical oncology (Northwood, London, England) · 2021Article
- Immune-related gene expression signatures in colorectal cancer.Oncology letters · 2021Article
- 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
- Key Disease Mechanisms Linked to Alzheimer's Disease in the Entorhinal Cortex.International journal of molecular sciences · 2021Article
- Correction of Niemann-Pick type C1 trafficking and activity with the histone deacetylase inhibitor valproic acid.The Journal of biological chemistry · 2020Article
- Amyloid precursor-like protein 2 interacts with claudin-7 and affects ovarian cancer cell survival.Future science OA · 2020Article
- Mitochondria-to-nucleus retrograde signaling drives formation of cytoplasmic chromatin and inflammation in senescence.Genes & development · 2020Article
- Hypoxia induced LUCAT1/PTBP1 axis modulates cancer cell viability and chemotherapy response.Molecular cancer · 2020Article
- Valproic acid-induced amphiregulin secretion confers resistance to temozolomide treatment in human glioma cells.BMC cancer · 2019Article
- Prospects for repurposing CNS drugs for cancer treatment.Oncology reviews · 2019Article
- Valproic acid exerts specific cellular and molecular anti-inflammatory effects in post-operative conjunctiva.Journal of molecular medicine (Berlin, Germany) · 2019Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The beta-amyloid precursor protein (APP) represents a type I transmembrane glycoprotein that is ubiquitously expressed. In the brain, it is a key player in the molecular pathogenesis of Alzheimer disease. Its physiological function is however less well understood. Previous studies showed that APP is up-regulated in prostate, colon, pancreatic tumor, and oral squamous cell carcinoma. In this study, we show that APP has an essential role in growth control of pancreatic and colon cancer. Abundant APP staining was found in human pancreatic adenocarcinoma and colon cancer tissue. Interestingly, treating pancreatic and colon cancer cells with valproic acid (VPA, 2-propylpentanoic acid), a known histone deacetylase (HDAC) inhibitor, leads to up-regulation of GRP78, an endoplasmic reticulum chaperone immunoglobulin-binding protein. GRP78 is involved in APP maturation and inhibition of tumor cell growth by down-regulation of APP and secreted soluble APPalpha. Trichostatin A, a pan-HDAC inhibitor, also lowered APP and increased GRP78 levels. In contrast, treating cells with valpromide, a VPA derivative lacking HDAC inhibitory properties, had no effect on APP levels. VPA did not modify the level of epidermal growth factor receptor, another type I transmembrane protein, and APLP2, a member of the APP family, demonstrating the specificity of the VPA effect on APP. Small interfering RNA-mediated knockdown of APP also resulted in significantly decreased cell growth. Based on these observations, the data suggest that APP down-regulation via HDAC inhibition provides a novel mechanism for pancreatic and colon cancer therapy.
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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.