{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T23:56:32Z","timestamp":1776815792365,"version":"3.51.2"},"reference-count":49,"publisher":"Spandidos Publications","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,5]]},"DOI":"10.3892\/or.2014.3091","type":"journal-article","created":{"date-parts":[[2014,3,14]],"date-time":"2014-03-14T12:47:14Z","timestamp":1394801234000},"page":"2422-2428","source":"Crossref","is-referenced-by-count":22,"title":["Arecoline inhibits epithelial cell viability by upregulating the apoptosis pathway: Implication for oral submucous fibrosis"],"prefix":"10.3892","volume":"31","author":[{"given":"MING","family":"LI","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"FENG","family":"GAO","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ZHONG-SU","family":"ZHOU","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"HUI-MING","family":"ZHANG","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"RUI","family":"ZHANG","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"YING-FANG","family":"WU","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MING-HAI","family":"BAI","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JI-JIA","family":"LI","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"SHI-RONG","family":"LIN","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JIE-YING","family":"PENG","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2249","published-online":{"date-parts":[[2014,3,14]]},"reference":[{"key":"key20180107222437_b1-or-31-05-2422","doi-asserted-by":"crossref","first-page":"199","DOI":"10.4103\/0973-1482.98970","article-title":"Pathogenesis of oral submucous fibrosis","volume":"8","author":"Khan","year":"2012","journal-title":"J Cancer Res Ther"},{"key":"key20180107222437_b2-or-31-05-2422","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.bjoms.2012.08.014","article-title":"Oral submucous fibrosis: an overview of the aetiology, pathogenesis, classification, and principles of management","volume":"51","author":"Arakeri","year":"2013","journal-title":"Br J Oral Maxillofacial Surg"},{"key":"key20180107222437_b3-or-31-05-2422","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1111\/j.1834-7819.1996.tb03136.x","article-title":"Oral submucous fibrosis. A review","volume":"41","author":"Cox","year":"1996","journal-title":"Aust Dent J"},{"key":"key20180107222437_b4-or-31-05-2422","first-page":"562","article-title":"Oral submucous fibrosis - a potentially malignant condition of growing concern","volume":"67","author":"Mahomed","year":"2012","journal-title":"SADJ"},{"key":"key20180107222437_b5-or-31-05-2422","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.oraloncology.2011.11.021","article-title":"Review of drug treatment of oral submucous fibrosis","volume":"48","author":"Chole","year":"2012","journal-title":"Oral Oncol"},{"key":"key20180107222437_b6-or-31-05-2422","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0300-9785(81)80026-9","article-title":"Oral submucous fibrosis","volume":"10","author":"Paissat","year":"1981","journal-title":"Int J Oral Surg"},{"key":"key20180107222437_b7-or-31-05-2422","first-page":"17","article-title":"Oral submucous fibrosis: an unusual disease","volume":"68","author":"Aziz","year":"1997","journal-title":"J N J Dent Assoc"},{"key":"key20180107222437_b8-or-31-05-2422","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1111\/j.1600-0714.2007.00582.x","article-title":"Nomenclature and classification of potentially malignant disorders of the oral mucosa","volume":"36","author":"Warnakulasuriya","year":"2007","journal-title":"J Oral Pathol Med"},{"key":"key20180107222437_b9-or-31-05-2422","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.oraloncology.2005.08.005","article-title":"Oral submucous fibrosis: review on aetiology and pathogenesis","volume":"42","author":"Tilakaratne","year":"2006","journal-title":"Oral Oncol"},{"key":"key20180107222437_b10-or-31-05-2422","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.oraloncology.2008.03.014","article-title":"Verrucous carcinoma of the oral cavity: a clinical and pathological study of 101 cases","volume":"45","author":"Walvekar","year":"2009","journal-title":"Oral Oncol"},{"key":"key20180107222437_b11-or-31-05-2422","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1002\/ijc.22304","article-title":"Betel quid not containing tobacco and oral cancer: a report on a case-control study in Papua New Guinea and a meta-analysis of current evidence","volume":"120","author":"Thomas","year":"2007","journal-title":"Int J Cancer"},{"key":"key20180107222437_b12-or-31-05-2422","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1111\/j.1600-0714.1995.tb01132.x","article-title":"Betel quid chewing, cigarette smoking and alcohol consumption related to oral cancer in Taiwan","volume":"24","author":"Ko","year":"1995","journal-title":"J Oral Pathol Med"},{"key":"key20180107222437_b13-or-31-05-2422","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/0165-7992(82)90029-X","article-title":"Chromosome-breaking ability of arecoline, a major betel-nut alkaloid, in mouse bone-marrow cells in vivo","volume":"103","author":"Panigrahi","year":"1982","journal-title":"Mutat Res"},{"key":"key20180107222437_b14-or-31-05-2422","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1002\/jcb.22137","article-title":"Arecoline-induced phosphorylated p53 and p21(WAF1) protein expression is dependent on ATM\/ATR and phosphatidylinositol-3-kinase in clone-9 cells","volume":"107","author":"Chou","year":"2009","journal-title":"J Cell Biochem"},{"key":"key20180107222437_b15-or-31-05-2422","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/0165-1218(81)90058-6","article-title":"Potentiation of genotoxicity by concurrent application of compounds found in betel quid: arecoline, eugenol, quercetin, chlorogenic acid and Mn2+","volume":"90","author":"Stich","year":"1981","journal-title":"Mutat Res"},{"key":"key20180107222437_b16-or-31-05-2422","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/S1368-8375(01)00003-3","article-title":"Role of areca nut in betel quid-associated chemical carcinogenesis: current awareness and future perspectives","volume":"37","author":"Jeng","year":"2001","journal-title":"Oral Oncol"},{"key":"key20180107222437_b17-or-31-05-2422","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.tox.2006.07.016","article-title":"Immunosuppression, hepatotoxicity and depression of antioxidant status by arecoline in albino mice","volume":"227","author":"Dasgupta","year":"2006","journal-title":"Toxicology"},{"key":"key20180107222437_b18-or-31-05-2422","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/S0959-440X(00)00146-9","article-title":"Caspases: key players in programmed cell death","volume":"10","author":"Grutter","year":"2000","journal-title":"Curr Opin Struct Biol"},{"key":"key20180107222437_b19-or-31-05-2422","first-page":"160","article-title":"Caspase-8 regulation of TRAIL-mediated cell death","volume":"34","author":"Crowder","year":"2012","journal-title":"Exp Oncol"},{"key":"key20180107222437_b20-or-31-05-2422","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/nrc883","article-title":"The Bcl2 family: regulators of the cellular life-or-death switch","volume":"2","author":"Cory","year":"2002","journal-title":"Nat Rev Cancer"},{"key":"key20180107222437_b21-or-31-05-2422","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/cyto.a.20819","article-title":"BH3-only proteins: the death-puppeteer\u2019s wires","volume":"77","author":"Ghiotto","year":"2010","journal-title":"Cytometry A"},{"key":"key20180107222437_b22-or-31-05-2422","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/nrm2952","article-title":"Mitochondria and cell death: outer membrane permeabilization and beyond","volume":"11","author":"Tait","year":"2010","journal-title":"Nat Rev Mol Cell Biol"},{"key":"key20180107222437_b23-or-31-05-2422","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.bbamcr.2011.01.026","article-title":"Caspase-8 and bid: caught in the act between death receptors and mitochondria","volume":"1813","author":"Kantari","year":"2011","journal-title":"Biochim Biophys Acta"},{"key":"key20180107222437_b24-or-31-05-2422","doi-asserted-by":"crossref","first-page":"2859","DOI":"10.1101\/gad.10.22.2859","article-title":"BID: a novel BH3 domain-only death agonist","volume":"10","author":"Wang","year":"1996","journal-title":"Genes Dev"},{"key":"key20180107222437_b25-or-31-05-2422","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S0092-8674(00)81590-1","article-title":"Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis","volume":"94","author":"Li","year":"1998","journal-title":"Cell"},{"key":"key20180107222437_b26-or-31-05-2422","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/S0092-8674(00)81589-5","article-title":"Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors","volume":"94","author":"Luo","year":"1998","journal-title":"Cell"},{"key":"key20180107222437_b27-or-31-05-2422","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1074\/jbc.274.2.1156","article-title":"Caspase cleaved BID targets mitochondria and is required for cytochrome c release, while BCL-XL prevents this release but not tumor necrosis factor-R1\/Fas death","volume":"274","author":"Gross","year":"1999","journal-title":"J Biol Chem"},{"key":"key20180107222437_b28-or-31-05-2422","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/j.1600-0714.1995.tb01175.x","article-title":"Oral cancer and precancer related to betel and miang chewing in Thailand: a review","volume":"24","author":"Reichart","year":"1995","journal-title":"J Oral Pathol Med"},{"key":"key20180107222437_b29-or-31-05-2422","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1080\/13556210120091482","article-title":"The oral health consequences of chewing areca nut","volume":"7","author":"Trivedy","year":"2002","journal-title":"Addict Biol"},{"key":"key20180107222437_b30-or-31-05-2422","first-page":"1","article-title":"Betel-quid and areca-nut chewing and some areca-nut derived nitrosamines","volume":"85","year":"2004","journal-title":"IARC Monogr Eval Carcinog Risks Hum"},{"key":"key20180107222437_b31-or-31-05-2422","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1093\/carcin\/bgt012","article-title":"Areca nut-induced buccal mucosa fibroblast contraction and its signaling: a potential role in oral submucous fibrosis - a precancer condition","volume":"34","author":"Chang","year":"2013","journal-title":"Carcinogenesis"},{"key":"key20180107222437_b32-or-31-05-2422","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1111\/j.1600-0714.2009.00758.x","article-title":"Arecoline and oral keratinocytes may affect the collagen metabolism of fibroblasts","volume":"38","author":"Li","year":"2009","journal-title":"J Oral Pathol Med"},{"key":"key20180107222437_b33-or-31-05-2422","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1111\/j.1601-0825.2006.01272.x","article-title":"Increased plasminogen activator inhibitor-1\/tissue type plasminogen activator ratio in oral submucous fibrosis","volume":"13","author":"Yang","year":"2007","journal-title":"Oral Dis"},{"key":"key20180107222437_b34-or-31-05-2422","doi-asserted-by":"crossref","first-page":"8489","DOI":"10.1158\/0008-5472.CAN-08-0823","article-title":"Up-regulation of inflammatory signalings by areca nut extract and role of cyclooxygenase-2-1195G>a polymorphism reveal risk of oral cancer","volume":"68","author":"Chiang","year":"2008","journal-title":"Cancer Res"},{"key":"key20180107222437_b35-or-31-05-2422","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/S1368-8375(03)00101-5","article-title":"Augmented mRNA expression of tissue inhibitor of metalloproteinase-1 in buccal mucosal fibroblasts by arecoline and safrole as a possible pathogenesis for oral submucous fibrosis","volume":"39","author":"Shieh","year":"2003","journal-title":"Oral Oncol"},{"key":"key20180107222437_b36-or-31-05-2422","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1111\/j.1600-0714.2004.00229.x","article-title":"Effects of arecoline, safrole, and nicotine on collagen phagocytosis by human buccal mucosal fibroblasts as a possible mechanism for oral submucous fibrosis in Taiwan","volume":"33","author":"Shieh","year":"2004","journal-title":"J Oral Pathol Med"},{"key":"key20180107222437_b37-or-31-05-2422","doi-asserted-by":"crossref","first-page":"e51806","DOI":"10.1371\/journal.pone.0051806","article-title":"Activation of TGF-beta pathway by areca nut constituents: a possible cause of oral submucous fibrosis","volume":"7","author":"Khan","year":"2012","journal-title":"PloS One"},{"key":"key20180107222437_b38-or-31-05-2422","doi-asserted-by":"crossref","first-page":"e12","DOI":"10.4317\/medoral.18226","article-title":"Expression of transforming growth factor beta and its correlation with lipodystrophy in oral submucous fibrosis: an immunohistochemical study","volume":"18","author":"Kale","year":"2013","journal-title":"Med Oral Patol Oral Cir Bucal"},{"key":"key20180107222437_b39-or-31-05-2422","doi-asserted-by":"crossref","first-page":"e55122","DOI":"10.1371\/journal.pone.0055122","article-title":"Elevation of S100A4 expression in buccal mucosal fibroblasts by arecoline: involvement in the pathogenesis of oral submucous fibrosis","volume":"8","author":"Yu","year":"2013","journal-title":"PloS One"},{"key":"key20180107222437_b40-or-31-05-2422","doi-asserted-by":"crossref","first-page":"e99","DOI":"10.1016\/j.oraloncology.2009.04.004","article-title":"Arecoline-stimulated connective tissue growth factor production in human buccal mucosal fibroblasts: modulation by curcumin","volume":"45","author":"Deng","year":"2009","journal-title":"Oral Oncol"},{"key":"key20180107222437_b41-or-31-05-2422","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1093\/carcin\/6.2.295","article-title":"Tobacco-specific and betel nut-specific N-nitroso compounds: occurrence in saliva and urine of betel quid chewers and formation in vitro by nitrosation of betel quid","volume":"6","author":"Nair","year":"1985","journal-title":"Carcinogenesis"},{"key":"key20180107222437_b42-or-31-05-2422","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1080\/01635588309513783","article-title":"Correlation of mutagenicity and tumorigenicity of betel quid and its ingredients","volume":"5","author":"Shirname","year":"1983","journal-title":"Nutr Cancer"},{"key":"key20180107222437_b43-or-31-05-2422","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1111\/j.1600-0714.2009.00881.x","article-title":"Salivary arecoline levels during areca nut chewing in human volunteers","volume":"39","author":"Cox","year":"2010","journal-title":"J Oral Pathol Med"},{"key":"key20180107222437_b44-or-31-05-2422","first-page":"5294","article-title":"Cytotoxic and genotoxic effects of areca nut-related compounds in cultured human buccal epithelial cells","volume":"49","author":"Sundqvist","year":"1989","journal-title":"Cancer Res"},{"key":"key20180107222437_b45-or-31-05-2422","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.tox.2005.07.026","article-title":"Prolonged exposure to arecoline arrested human KB epithelial cell growth: regulatory mechanisms of cell cycle and apoptosis","volume":"220","author":"Lee","year":"2006","journal-title":"Toxicology"},{"key":"key20180107222437_b46-or-31-05-2422","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1007\/s00784-011-0604-1","article-title":"Arecoline induced cell cycle arrest, apoptosis, and cytotoxicity to human endothelial cells","volume":"16","author":"Tseng","year":"2012","journal-title":"Clin Oral Investig"},{"key":"key20180107222437_b47-or-31-05-2422","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.3892\/or.2013.2360","article-title":"Arecoline suppresses HaCaT cell proliferation through cell cycle regulatory molecules","volume":"29","author":"Zhou","year":"2013","journal-title":"Oncol Rep"},{"key":"key20180107222437_b48-or-31-05-2422","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1016\/j.freeradbiomed.2010.07.017","article-title":"Arecoline, a major alkaloid of the areca nut, causes neurotoxicity through enhancement of oxidative stress and suppression of the antioxidant protective system","volume":"49","author":"Shih","year":"2010","journal-title":"Free Radic Biol Med"},{"key":"key20180107222437_b49-or-31-05-2422","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/1476-4598-9-126","article-title":"Arecoline induces HA22T\/VGH hepatoma cells to undergo anoikis - involvement of STAT3 and RhoA activation","volume":"9","author":"Cheng","year":"2010","journal-title":"Mol Cancer"}],"container-title":["Oncology Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/spandidos-publications.com\/10.3892\/or.2014.3091\/download","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,25]],"date-time":"2024-05-25T00:43:24Z","timestamp":1716597804000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.spandidos-publications.com\/10.3892\/or.2014.3091"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3,14]]},"references-count":49,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2014,3,14]]},"published-print":{"date-parts":[[2014,5]]}},"alternative-id":["10.3892\/or.2014.3091"],"URL":"https:\/\/doi.org\/10.3892\/or.2014.3091","relation":{},"ISSN":["1021-335X","1791-2431"],"issn-type":[{"value":"1021-335X","type":"print"},{"value":"1791-2431","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3,14]]}}}