ArticleOncotarget2016
Acquisition cancer stemness, mesenchymal transdifferentiation, and chemoresistance properties by chronic exposure of oral epithelial cells to arecoline.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 40 citations in OpenAlex.
- The multistep progression of areca nut-induced oral cancer: a mechanistic roadmap from pathogenesis to precision therapy.Life medicine · 2026Review
- From Environmental Risk to Cancer Stemness: Epigenetic Regulation in Oral Squamous Cell Carcinoma.Pharmaceuticals (Basel, Switzerland) · 2026Review
- 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
- Article
- Role of Stem Cells in the Pathogenesis and Malignant Transformation of Oral Submucous Fibrosis.Stem cell reviews and reports · 2024Review
- Differential Expression of MicroRNA MiR-145 and MiR-155 Downstream Targets in Oral Cancers Exhibiting Limited Chemotherapy Resistance.International journal of molecular sciences · 2024Article
- Comprehensive insights into areca nut: active components and omics technologies for bioactivity evaluation and quality control.Frontiers in pharmacology · 2024Review
- 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
- Clinicopathological Significance of Cancer Stem Cell Markers (OCT-3/4 and SOX-2) in Oral Submucous Fibrosis and Oral Squamous Cell Carcinoma.Biomedicines · 2023Article
- α-Mangostin Inhibits the Activation of Myofibroblasts via Downregulation of Linc-ROR-Mediated TGFB1/Smad Signaling.Nutrients · 2023Article
- Carcinogenic Effects of Areca Nut and Its Metabolites: A Review of the Experimental Evidence.Clinics and practice · 2023Review
- Cancer stem cells of head and neck squamous cell carcinoma; distance towards clinical application; a systematic review of literature.American journal of cancer research · 2023Review
- Identification of a BRAF/PA28γ/MEK1 signaling axis and its role in epithelial-mesenchymal transition in oral submucous fibrosis.Cell death & disease · 2022Article
- Interferon-inducible protein, IFIX, has tumor-suppressive effects in oral squamous cell carcinoma.Scientific reports · 2021Article
- Fat mass and obesity-associated protein regulates tumorigenesis of arecoline-promoted human oral carcinoma.Cancer medicine · 2021Article
- JunD accentuates arecoline-induced disruption of tight junctions and promotes epithelial-to-mesenchymal transition by association with NEAT1 lncRNA.Oncotarget · 2021Article
- Triphala extract negates arecoline-induced senescence in oral mucosal epithelial cells in vitro.Saudi journal of biological sciences · 2021Article
- Suppression of poised oncogenes by ZMYND8 promotes chemo-sensitization.Cell death & disease · 2020Article
- Arecoline suppresses epithelial cell viability by upregulating tropomyosin-1 through the transforming growth factor-β/Smad pathway.Pharmaceutical biology · 2020Article
- Analysis of risk factors for multiple primary oral squamous cell carcinoma: a cohort study.Clinical oral investigations · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oral squamous cell carcinoma (OSCC), one of the most deadliest malignancies in the world, is caused primarily by areca nut chewing in Southeast Asia. The mechanisms by which areca nut participates in OSCC tumorigenesis are not well understood. In this study, we investigated the effects of low dose long-term arecoline (10 μg/mL, 90-days), a major areca nut alkaloid, on enhancement cancer stemness of human oral epithelial (OE) cells. OE cells with chronic arecoline exposure resulted in increased ALDH1 population, CD44 positivity, stemness-related transcription factors (Oct4, Nanog, and Sox2), epithelial-mesenchymal transdifferentiation (EMT) traits, chemoresistance, migration/invasiveness/anchorage independent growth and in vivo tumor growth as compared to their untreated controls. Mechanistically, ectopic miR-145 over-expression in chronic arecoline-exposed OE (AOE) cells inhibited the cancer stemness and xenografic. In AOE cells, luciferase reporter assays further revealed that miR-145 directly targets the 3' UTR regions of Oct4 and Sox2 and overexpression of Sox2/Oct4 effectively reversed miR-145-regulated cancer stemness-associated phenomenas. Additionally, clinical results further revealed that Sox2 and Oct4 expression was inversely correlated with miR-145 in the tissues of areca quid chewing-associated OSCC patients. This study hence attempts to provide novel insight into areca nut-induced oral carcinogenesis and new intervention for the treatment of OSCC patients, especially in areca nut users.
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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.