ArticleJournal of cellular physiology2019
Arecoline N-oxide regulates oral squamous cell carcinoma development through NOTCH1 and FAT1 expressions.
Article in Journal of cellular physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 2 of them syntheses that pooled it.
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Who cites it
16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 21 citations in OpenAlex.
- Models of Oral Epithelial Dysplasia: A Systematic Review and Temporal Analysis.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2026Pooled it
- Pooled it
- The multistep progression of areca nut-induced oral cancer: a mechanistic roadmap from pathogenesis to precision therapy.Life medicine · 2026Review
- Drug repurposing targeting miRNA-mRNA networks to mitigate areca nut-induced head and neck cancer.Biomedical journal · 2026Article
- Mechanistic Insights into Astragalus Membranaceus for Oral Submucosal Fibrosis: A Network Pharmacology and Experimental Approach.Current pharmaceutical design · 2026Article
- Diagnostic potential of salivary IL-1β, IL-8, SAT, S100P, and OAZ1 in oral squamous cell carcinoma, oral submucous fibrosis, and oral lichen planus based on findings from a Sri Lankan cohort.Scientific reports · 2024Article
- 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
- Exploring Possible Diagnostic Precancerous Biomarkers for Oral Submucous Fibrosis: A Narrative Review.Cancers · 2023Review
- Evaluating Alterations of the Oral Microbiome and Its Link to Oral Cancer among Betel Quid Chewers: Prospecting Reversal through Probiotic Intervention.Pathogens (Basel, Switzerland) · 2023Review
- Oxidative Stress and Endoplasmic Reticulum Stress Contributes to Arecoline and Its Secondary Metabolites-Induced Dyskinesia in Zebrafish Embryos.International journal of molecular sciences · 2023Article
- 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
- Mouse Models for Immune Checkpoint Blockade Therapeutic Research in Oral Cancer.International journal of molecular sciences · 2022Review
- Genetic toxicology and toxicokinetics of arecoline and related areca nut compounds: an updated review.Archives of toxicology · 2021Review
- Comprehensive Analysis of the Effects of Genetic Ancestry and Genetic Characteristics on the Clinical Evolution of Oral Squamous Cell Carcinoma.Frontiers in cell and developmental biology · 2021Article
- Identification of novel biomarkers and candidate small molecule drugs in rheumatoid arthritis and osteoarthritis based on bioinformatics analysis of high-throughput data.Bioscience reports · 2020Article
- Mouse Tumor-Bearing Models as Preclinical Study Platforms for Oral Squamous Cell Carcinoma.Frontiers in oncology · 2020Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Areca nut has been evaluated as a group I carcinogen to humans. However, the exact compounds of areca nut causing oral cancer remain unproven. Previous findings from our lab revealed that arecoline N-oxide (ANO), a metabolite of arecoline, exhibits an oral fibrotic effect in immune-deficient NOD/SCID mice. The aim of this study is to investigate the oral potentially malignant disorders (OPMD) inductive activity between areca-alkaloid arecoline and its metabolite ANO in C57BL/6 mice. Our findings show that ANO showed higher activity in inducing hyperplasia with leukoplakia and collagen deposition in C57BL/6 mice compared with the arecoline treated groups. Importantly, immunohistochemical studies showed significant upregulation of NOTCH1, HES1, FAT1, PCNA, and Ki67 expressions in the pathological hyperplastic part. In addition, in vitro studies showed that upregulation of NOTCH1 and FAT1 expressions in ANO treated HGF-1 and DOK cell models. We found that NOTCH1 regulates TP53 expression from NOTCH1 knockdown oral cancer cells. The DNA damage was significantly increased after arecoline and ANO treatment. Further, we found that arecoline-induced H2AX expression was regulated by FMO3. Altogether, our findings show that ANO exhibited higher toxicity in OPMD activity and play a significant role in the induction of areca nut mediated oral tumorigenesis.
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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.