ArticleCarcinogenesis2013
Omega-3 polyunsaturated fatty acids selectively inhibit growth in neoplastic oral keratinocytes by differentially activating ERK1/2.
Article in Carcinogenesis, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
20 citing papers in PubMed, 48 citations in OpenAlex.
- Association between red blood cell fatty acids composition and risk of esophageal cancer: a hospital-based case-control study.Lipids in health and disease · 2025Article
- RNAi-based ALOX15B silencing augments keratinocyte inflammation in vitro via EGFR/STAT1/JAK1 signalling.Cell death & disease · 2025Article
- Fatty acids and epigenetics in health and diseases.Food science and biotechnology · 2024Review
- The Influences of Omega-3 Polyunsaturated Fatty Acids on the Development of Skin Cancers.Diagnostics (Basel, Switzerland) · 2021Review
- Role of Key Micronutrients from Nutrigenetic and Nutrigenomic Perspectives in Cancer Prevention.Medicina (Kaunas, Lithuania) · 2019Review
- Group IID, IIE, IIF and III secreted phospholipase ABiochimica et biophysica acta. Molecular and cell biology of lipids · 2019Review
- Fatty acids distribution and content in oral squamous cell carcinoma tissue and its adjacent microenvironment.PloS one · 2019Article
- EPA significantly improves anti-EGFR targeted therapy by regulating miR-378 expression in colorectal cancer.Oncology letters · 2018Article
- The induction of the fibroblast extracellular senescence metabolome is a dynamic process.Scientific reports · 2018Article
- Bio-Guided Fractionation of Papaya Leaf Juice for Delineating the Components Responsible for the Selective Anti-proliferative Effects on Prostate Cancer Cells.Frontiers in pharmacology · 2018Article
- Phospholipase AInflammation and regeneration · 2018Review
- Review
- Secretory phospholipase-A2 and fatty acid composition in oral reactive lesions: a cross-sectional study.Cancer cell international · 2017Article
- Replicatively senescent human fibroblasts reveal a distinct intracellular metabolic profile with alterations in NAD+ and nicotinamide metabolism.Scientific reports · 2016Article
- Docosahexaenoic Acid Induces Oxidative DNA Damage and Apoptosis, and Enhances the Chemosensitivity of Cancer Cells.International journal of molecular sciences · 2016Review
- Omega-3 Fatty Acids and Cancer Cell Cytotoxicity: Implications for Multi-Targeted Cancer Therapy.Journal of clinical medicine · 2016Review
- Fat-1 gene inhibits human oral squamous carcinoma cell proliferation through downregulation of β-catenin signaling pathways.Experimental and therapeutic medicine · 2016Article
- The cytotoxicity of BAMLET complexes is due to oleic acid and independent of the α-lactalbumin component.FEBS open bio · 2015Article
- Association of cancer metabolism-related proteins with oral carcinogenesis - indications for chemoprevention and metabolic sensitizing of oral squamous cell carcinoma?Journal of translational medicine · 2014Article
- The targeting mechanism of DHA ligand and its conjugate with Gemcitabine for the enhanced tumor therapy.Oncotarget · 2014Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs)-eicosapentaenoic acid (EPA) and its metabolite docosahexaenoic acid (DHA)-inhibit cancer formation in vivo, but their mechanism of action is unclear. Extracellular signal-regulated kinase 1/2 (ERK1/2) activation and inhibition have both been associated with the induction of tumour cell apoptosis by n-3 PUFAs. We show here that low doses of EPA, in particular, inhibited the growth of premalignant and malignant keratinocytes more than the growth of normal counterparts by a combination of cell cycle arrest and apoptosis. The growth inhibition of the oral squamous cell carcinoma (SCC) lines, but not normal keratinocytes, by both n-3 PUFAs was associated with epidermal growth factor receptor (EGFR) autophosphorylation, a sustained phosphorylation of ERK1/2 and its downstream target p90RSK but not with phosphorylation of the PI3 kinase target Akt. Inhibition of EGFR with either the EGFR kinase inhibitor AG1478 or an EGFR-blocking antibody inhibited ERK1/2 phosphorylation, and the blocking antibody partially antagonized growth inhibition by EPA but not by DHA. DHA generated more reactive oxygen species and activated more c-jun N-terminal kinase than EPA, potentially explaining its increased toxicity to normal keratinocytes. Our results show that, in part, EPA specifically inhibits SCC growth and development by creating a sustained signalling imbalance to amplify the EGFR/ERK/p90RSK pathway in neoplastic keratinocytes to a supraoptimal level, supporting the chemopreventive potential of EPA, whose toxicity to normal cells might be reduced further by blocking its metabolism to DHA. Furthermore, ERK1/2 phosphorylation may have potential as a biomarker of n-3 PUFA function in vivo.
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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.