ArticleJournal of cellular and molecular medicine2015
Epithelial atrophy in oral submucous fibrosis is mediated by copper (II) and arecoline of areca nut.
Article in Journal of cellular and molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 49 citations in OpenAlex.
- The METTL3/LOXL2 axis participates in aberrant epithelial-fibroblast crosstalk and induces oral submucous fibrosis in rats.Molecular and cellular biochemistry · 2026Article
- Scientific Mapping and Knowledge Evolution of Global Areca Research.International dental journal · 2026Review
- Molecular and microenvironmental drivers of malignant transformation from oral potentially malignant disorders to oral squamous cell carcinoma.Frontiers in oncology · 2026Review
- Periodontitis presenting among betel quid users: A case series.Clinical advances in periodontics · 2025Article
- PDGF-BB promotes oral submucosal fibrosis by driving phenotypic transformation and autophagy in oral mucosal fibroblasts through downregulation of circHIPK3.Scientific reports · 2025Article
- Estimation of serum levels of mast cells-related chymase, histamine and diamine oxidase in oral submucous fibrosis- a preliminary report.BMC oral health · 2025Article
- Role of Stem Cells in the Pathogenesis and Malignant Transformation of Oral Submucous Fibrosis.Stem cell reviews and reports · 2024Review
- Stromal thrombospondin 1 suppresses angiogenesis in oral submucous fibrosis.International journal of oral science · 2024Article
- Mechanism of adipose tissue-derived stromal cell-extracellular vesicles in treating oral submucous fibrosis by blocking the TGF-β1/Smad3 pathway via the miR-760-3p/IGF1R axis.Biomolecules & biomedicine · 2023Article
- A Critical Interpretive Synthesis of the Role of Arecoline in Oral Carcinogenesis: Is the Local Cholinergic Axis a Missing Link in Disease Pathophysiology?Pharmaceuticals (Basel, Switzerland) · 2023Review
- Mast cell expression in oral submucous fibrosis: A systematic review and metanalysis.Journal of clinical and experimental dentistry · 2023Review
- Genetic and epigenetic instability induced by betel quid associated chemicals.Toxicology reports · 2023Review
- Jiawei Danxuan Koukang Alleviates Arecoline Induced Oral Mucosal Lesions: Network Pharmacology and the Combined Ultra-High Performance Liquid Chromatography (UPLC) and Mass Spectrometry (MS).Drug design, development and therapy · 2023Article
- Insulin-like Growth Factor-2 (IGF-2) in Fibrosis.Biomolecules · 2022Review
- A Comprehensive Analysis of the Role of Oxidative Stress in the Pathogenesis and Chemoprevention of Oral Submucous Fibrosis.Antioxidants (Basel, Switzerland) · 2022Review
- Triphala extract negates arecoline-induced senescence in oral mucosal epithelial cells in vitro.Saudi journal of biological sciences · 2021Article
- Macro-, micro-, and trace element distributions in areca nut, husk, and soil of northeast India.Environmental monitoring and assessment · 2021Article
- Arecoline suppresses epithelial cell viability by upregulating tropomyosin-1 through the transforming growth factor-β/Smad pathway.Pharmaceutical biology · 2020Article
- Loss of oral mucosal stem cell markers in oral submucous fibrosis and their reactivation in malignant transformation.International journal of oral science · 2020Review
- The Protective Effect of Antioxidants in Areca Nut Extract-Induced Oral Carcinogenesis.Asian Pacific journal of cancer prevention : APJCP · 2020Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exposure of oral cavity to areca nut is associated with several pathological conditions including oral submucous fibrosis (OSF). Histopathologically OSF is characterized by epithelial atrophy, chronic inflammation, juxtaepithelial hyalinization, leading to fibrosis of submucosal tissue and affects 0.5% of the population in the Indian subcontinent. As the molecular mechanisms leading to atrophied epithelium and fibrosis are poorly understood, we studied areca nut actions on human keratinocyte and gingival fibroblast cells. Areca nut water extract (ANW) was cytotoxic to epithelial cells and had a pro-proliferative effect on fibroblasts. This opposite effect of ANW on epithelial and fibroblast cells was intriguing but reflects the OSF histopathology such as epithelial atrophy and proliferation of fibroblasts. We demonstrate that the pro-proliferative effects of ANW on fibroblasts are dependent on insulin-like growth factor signalling while the cytotoxic effects on keratinocytes are dependent on the generation of reactive oxygen species. Treatment of keratinocytes with arecoline which is a component of ANW along with copper resulted in enhanced cytotoxicity which becomes comparable to IC(50) of ANW. Furthermore, studies using cyclic voltammetry, mass spectrometry and plasmid cleavage assay suggested that the presence of arecoline increases oxidation reduction potential of copper leading to enhanced cleavage of DNA which could generate an apoptotic response. Terminal deoxynucleotidyl transferase dUTP Nick End Labeling assay and Ki-67 index of OSF tissue sections suggested epithelial apoptosis, which could be responsible for the atrophy of OSF epithelium.
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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.