ArticlePloS one2014
Areca nut components affect COX-2, cyclin B1/cdc25C and keratin expression, PGE2 production in keratinocyte is related to reactive oxygen species, CYP1A1, Src, EGFR and Ras signaling.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 38 citations in OpenAlex.
- [Efficacy of curcumin in the treatment of oral submucous fibrosis: a Meta-analysis].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2021Pooled it
- Betel nut chewing and the risk of chronic kidney disease: evidence from a meta-analysis.International urology and nephrology · 2018Pooled it
- Article
- The multistep progression of areca nut-induced oral cancer: a mechanistic roadmap from pathogenesis to precision therapy.Life medicine · 2026Review
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- The Role of Klotho in Oral and Maxillofacial Diseases: Mechanisms and Research Progress.Biomolecules · 2025Review
- Article
- Overlap in oncogenic and pro-inflammatory pathways associated with areca nut and nicotine exposure.Cancer pathogenesis and therapy · 2024Article
- Carcinogenic Effects of Areca Nut and Its Metabolites: A Review of the Experimental Evidence.Clinics and practice · 2023Review
- Curcumin and its Analogs and Carriers: Potential Therapeutic Strategies for Human Osteosarcoma.International journal of biological sciences · 2023Review
- A Comprehensive Analysis of the Role of Oxidative Stress in the Pathogenesis and Chemoprevention of Oral Submucous Fibrosis.Antioxidants (Basel, Switzerland) · 2022Review
- Arecoline induces epithelial-mesenchymal transformation and promotes metastasis of oral cancer by SAA1 expression.Cancer science · 2021Article
- Identification of an immune classification for cervical cancer and integrative analysis of multiomics data.Journal of translational medicine · 2021Article
- Signaling pathways promoting epithelial mesenchymal transition in oral submucous fibrosis and oral squamous cell carcinoma.The Japanese dental science review · 2020Review
- Loss of oral mucosal stem cell markers in oral submucous fibrosis and their reactivation in malignant transformation.International journal of oral science · 2020Review
- Article
- How Each Component of Betel Quid Is Involved in Oral Carcinogenesis: Mutual Interactions and Synergistic Effects with Other Carcinogens-a Review Article.Current oncology reports · 2019Review
- Effectors of thioredoxin reductase: Brevetoxins and manumycin-A.Comparative biochemistry and physiology. Toxicology & pharmacology : CBP · 2019Article
- Multifaceted Mechanisms of Areca Nuts in Oral Carcinogenesis: the Molecular Pathology from Precancerous Condition to Malignant Transformation.Journal of Cancer · 2019Review
- Manumycin A Is a Potent Inhibitor of Mammalian Thioredoxin Reductase-1 (TrxR-1).ACS medicinal chemistry letters · 2018Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsChewing of betel quid (BQ) increases the risk of oral cancer and oral submucous fibrosis (OSF), possibly by BQ-induced toxicity and induction of inflammatory response in oral mucosa.
methodsPrimary gingival keratinocytes (GK cells) were exposed to areca nut (AN) components with/without inhibitors. Cytotoxicity was measured by 3-(4,5-dimethyl- thiazol- 2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. mRNA and protein expression was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting. PGE2/PGF2α production was measured by enzyme-linked immunosorbent assays.
resultsAreca nut extract (ANE) stimulated PGE2/PGF2α production, and upregulated the expression of cyclooxygenase-2 (COX-2), cytochrome P450 1A1 (CYP1A1) and hemeoxygenase-1 (HO-1), but inhibited expression of keratin 5/14, cyclinB1 and cdc25C in GK cells. ANE also activated epidermal growth factor receptor (EGFR), Src and Ras signaling pathways. ANE-induced COX-2, keratin 5, keratin 14 and cdc25C expression as well as PGE2 production were differentially regulated by α-naphthoflavone (a CYP 1A1/1A2 inhibitor), PD153035 (EGFR inhibitor), pp2 (Src inhibitor), and manumycin A (a Ras inhibitor). ANE-induced PGE2 production was suppressed by piper betle leaf (PBL) extract and hydroxychavicol (two major BQ components), dicoumarol (a NAD(P)H: Quinone Oxidoreductase--NQO1 inhibitor) and curcumin. ANE-induced cytotoxicity was inhibited by catalase and enhanced by dicoumarol, suggesting that AN components may contribute to the pathogenesis of OSF and oral cancer via induction of aberrant differentiation, cytotoxicity, COX-2 expression, and PGE2/PGF2α production.
conclusionsCYP4501A1, reactive oxygen species (ROS), EGFR, Src and Ras signaling pathways could all play a role in ANE-induced pathogenesis of oral cancer. Addition of PBL into BQ and curcumin consumption could inhibit the ANE-induced inflammatory response.
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Registered trials
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