ArticleOncotarget2016
Areca nut components stimulate ADAM17, IL-1α, PGE2 and 8-isoprostane production in oral keratinocyte: role of reactive oxygen species, EGF and JAK signaling.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Betel nut chewing and the risk of chronic kidney disease: evidence from a meta-analysis.International urology and nephrology · 2018Pooled it
- Fibrotic-Angiogenic Signaling Networks in Oral Submucous Fibrosis: Pathobiology and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Article
- Mechanistic Insights into Astragalus Membranaceus for Oral Submucosal Fibrosis: A Network Pharmacology and Experimental Approach.Current pharmaceutical design · 2026Article
- Molecular mechanisms of therapeutic resistance in areca nut-associated oral squamous cell carcinoma: the interplay of chronic inflammation and epithelial-mesenchymal transition.Frontiers in oncology · 2026Review
- Synthesis and biological evaluation ofJournal of enzyme inhibition and medicinal chemistry · 2024Article
- Mechanism of mangiferin in the treatment of oral submucous fibrosis based on Gene Expression Omnibus database chip mining combined with network pharmacology and molecular docking.Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2024Article
- Computational analysis of phytocompounds inHeliyon · 2024Article
- Potential impact of ADAM-10 genetic variants with the clinical features of oral squamous cell carcinoma.Journal of cellular and molecular medicine · 2023Article
- A Comprehensive Analysis of the Role of Oxidative Stress in the Pathogenesis and Chemoprevention of Oral Submucous Fibrosis.Antioxidants (Basel, Switzerland) · 2022Review
- The World of Oral Cancer and Its Risk Factors Viewed from the Aspect of MicroRNA Expression Patterns.Genes · 2022Review
- Molecular Mechanisms of Malignant Transformation of Oral Submucous Fibrosis by Different Betel Quid Constituents-Does Fibroblast Senescence Play a Role?International journal of molecular sciences · 2022Review
- Squamous cell cancer of the temporal bone: a review of the literature.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2021Review
- Effect of MACC1 Genetic Polymorphisms and Environmental Risk Factors in the Occurrence of Oral Squamous Cell Carcinoma.Journal of personalized medicine · 2021Article
- Pan-cancer analysis reveals tumor-associated macrophage communication in the tumor microenvironment.Experimental hematology & oncology · 2021Article
- Arecoline suppresses epithelial cell viability by upregulating tropomyosin-1 through the transforming growth factor-β/Smad pathway.Pharmaceutical biology · 2020Article
- Perception and belief in oral health among Karen ethnic group living along Thai-Myanmar border, Thailand.BMC oral health · 2020Article
- The Protective Effect of Antioxidants in Areca Nut Extract-Induced Oral Carcinogenesis.Asian Pacific journal of cancer prevention : APJCP · 2020Article
- Role and Mechanism of LIF in Oral Squamous Cell Carcinoma Progression.Journal of clinical medicine · 2020Article
- Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Betel quid (BQ) chewing is an etiologic factor of oral submucous fibrosis (OSF) and oral cancer. There are 600 million BQ chewers worldwide. The mechanisms for the toxic and inflammatory responses of BQ are unclear. In this study, both areca nut (AN) extract (ANE) and arecoline stimulated epidermal growth factor (EGF) and interleukin-1α (IL-1α) production of gingival keratinocytes (GKs), whereas only ANE can stimulate a disintegrin and metalloproteinase 17 (ADAM17), prostaglandin E2 (PGE2) and 8-isoprostane production. ANE-induced EGF production was inhibited by catalase. Addition of anti-EGF neutralizing antibody attenuated ANE-induced cyclooxygenase-2 (COX-2), mature ADAM9 expression and PGE2 and 8-isoprostane production. ANE-induced IL-1α production was inhibited by catalase, anti-EGF antibody, PD153035 (EGF receptor antagonist) and U0126 (MEK inhibitor) but not by α-naphthoflavone (cytochrome p450-1A1 inhibitor). ANE-induced ADAM17 production was inhibited by pp2 (Src inhibitor), U0126, α-naphthoflavone and aspirin. AG490 (JAK inhibitor) prevented ANE-stimulated ADAM17, IL-1α, PGE2 production, COX-2 expression, ADAM9 maturation, and the ANE-induced decline in keratin 5 and 14, but showed little effect on cdc2 expression and EGF production. Moreover, ANE-induced 8-isoprostane production by GKs was inhibited by catalase, anti-EGF antibody, AG490, pp2, U0126, α-naphthoflavone, Zinc protoporphyrin (ZnPP) and aspirin. These results indicate that AN components may involve in BQ-induced oral cancer by induction of reactive oxygen species, EGF/EGFR, IL-1α, ADAMs, JAK, Src, MEK/ERK, CYP1A1, and COX signaling pathways, and the aberration of cell cycle and differentiation. Various blockers against ROS, EGF, IL-1α, ADAM, JAK, Src, MEK, CYP1A1, and COX can be used for prevention or treatment of BQ chewing-related diseases.
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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.