ArticleAging2019
Stimulation of MMP-9 of oral epithelial cells by areca nut extract is related to TGF-β/Smad2-dependent and -independent pathways and prevented by betel leaf extract, hydroxychavicol and melatonin.
Article in Aging, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 20 citations in OpenAlex.
- The multistep progression of areca nut-induced oral cancer: a mechanistic roadmap from pathogenesis to precision therapy.Life medicine · 2026Review
- Impact of red-lime and white-lime betel quid on oral cell lines: Cytotoxicity and effects on fibronectin and type I collagen expression.Journal of dental sciences · 2025Article
- Hydroxychavicol as a potential anticancer agent (Review).Oncology letters · 2023Review
- Potential of melatonin to reverse epigenetic aberrations in oral cancer: new findings.EXCLI journal · 2023Review
- Melatonin exerts anti-fibrinolytic effects by regulating IL-1β-induced changes in uPA, uPAR, and PAI-1 expression/production in human dental pulp cells.Journal of food and drug analysis · 2022Article
- Melatonin Inhibits Osteoclastogenesis and Osteolytic Bone Metastasis: Implications for Osteoporosis.International journal of molecular sciences · 2021Review
- Article
- Comparative Analysis of Cytokine Expression in Oral Keratinocytes and THP-1 Macrophages in Response to the Most Prevalent Serotypes ofMicroorganisms · 2021Article
- Genetic Susceptibility and Protein Expression of Extracellular Matrix Turnover-Related Genes in Oral Submucous Fibrosis.International journal of molecular sciences · 2020Review
- Melatonin Inhibits the Progression of Oral Squamous Cell CarcinomaFrontiers in oncology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThere are 200-600 million betel quid (BQ) chewers in the world. BQ increases oral cancer risk. Matrix metalloproteinase-9 (MMP-9) is responsible for matrix degradation, cancer invasion and metastasis. Whether areca nut extract (ANE), a BQ component, stimulates MMP-9 secretion, and the related signaling pathways awaits investigation.
resultsANE (but not arecoline) stimulated MMP-9 production of gingival keratinocytes and SAS cancer epithelial cells. ANE stimulated TGF-β1, p-Smad2, and p-TAK1 protein expression. ANE-induced MMP-9 production/expression in SAS cells can be attenuated by SB431542 (ALK5/Smad2 inhibitor), 5Z-7-Oxozeaenol (TAK1 inhibitor), catalase, PD153035 (EGFR tyrosine kinase inhibitor), AG490 (JAK inhibitor), U0126 (MEK/ERK inhibitor), LY294002 (PI3K/Akt inhibitor), betel leaf (PBL) extract, and hydroxychavicol (HC, a PBL component), and melatonin, but not by aspirin.
conclusionsAN components contribute to oral carcinogenesis by stimulating MMP-9 secretion, thus enhancing tumor invasion/metastasis. These events are related to reactive oxygen species, TGF-β1, Smad2-dependent and -independent signaling, but not COX. These signaling molecules can be biomarkers of BQ carcinogenesis. PBL, HC and melatonin and other targeting therapy can be used for oral cancer treatment.
methodsANE-induced MMP-9 expression/secretion of oral epithelial cells and related TGF-β1, Smad-dependent and -independent signaling were studied by MTT assay, RT-PCR, western blotting, immunofluorescent staining, and ELISA.
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