{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T05:36:24Z","timestamp":1778132184568,"version":"3.51.4"},"reference-count":39,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2012,8,21]],"date-time":"2012-08-21T00:00:00Z","timestamp":1345507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Head &amp; Neck"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>There are 600 million betel quid chewers around the world. betel quid chewing is a major risk factor of oral cancer. Why betel quid components induce oral cancer is not clear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cytotoxicity of areca nut extract and arecoline (an areca nut alkaloid) to SAS oral epithelial cell line was evaluated by trypan blue dye exclusion and MTT assays. Cell cycle distribution and apoptosis was analyzed by propidium iodide staining flow cytometry. Chk1 and chk2 activation was analyzed by Pathscan phospho\u2010enzyme\u2010linked immunosorbent assay. Metalloproteinase\u20109 (MMP\u20109), tissue inhibitors of metalloproteinase (TIMPs) production was measured by enzyme\u2010linked immunosorbent assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Areca nut extract (800 \u03bcg\/mL) and arecoline (&gt;0.4 mmol\/L) caused cell death, apoptosis, and cell cycle arrest of SAS cells. Areca nut extract and arecoline stimulated Chk1 and Chk2 phosphorylation in SAS cells. Areca nut extract stimulated cellular MMP\u20109 but suppressed TIMP\u20101 and TIMP\u20102 production.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Areca nut components activate Chk1\/Chk2, alter cell cycle regulation\/apoptosis, MMP\u20109, and TIMPs production, contributing to the pathogenesis of oral carcinogenesis. \u00a9 2012 Wiley Periodicals, Inc. Head Neck, 2013<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hed.23119","type":"journal-article","created":{"date-parts":[[2012,8,21]],"date-time":"2012-08-21T05:05:45Z","timestamp":1345525545000},"page":"1295-1302","source":"Crossref","is-referenced-by-count":24,"title":["Toxicity of areca nut ingredients: Activation of CHK1\/CHK2, induction of cell cycle arrest, and regulation of MMP\u20109 and TIMPs production in SAS epithelial cells"],"prefix":"10.1002","volume":"35","author":[{"given":"Mei\u2010Chi","family":"Chang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiu\u2010Po","family":"Chan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei\u2010Ting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bei\u2010En","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jang\u2010Jaer","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuei\u2010Kuen","family":"Tseng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sin\u2010Yuet","family":"Yeung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang\u2010Jiunn","family":"Hahn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiiang\u2010Huei","family":"Jeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,8,21]]},"reference":[{"key":"e_1_2_6_2_2","volume-title":"Bureau of Health Promotion","author":"DOH new cancer cases report","year":"2008"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.1995.tb01132.x"},{"key":"e_1_2_6_4_2","first-page":"1","article-title":"Betel\u2010quid and areca\u2010nut chewing and some areca\u2010nut\u2010derived nitrosamines\u2014summary of data reported and evaluation","volume":"85","author":"IARC","year":"2004","journal-title":"IARC Monographs on the Evaluation of Carcinogenic Risks to Humans"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.1992.tb01007.x"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1368-8375(01)00003-3"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2006.08.010"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2005.08.005"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2010.06.006"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2008.05.007"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2006.06.029"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20333"},{"key":"e_1_2_6_13_2","doi-asserted-by":"crossref","first-page":"50676","DOI":"10.1074\/jbc.M404465200","article-title":"The induction of prostaglandin E2 production, interleukin\u20106 production, cell cycle arrest and cytotoxicity in primary oral keratinocytes and KB cancer cells by areca nut ingredients is differentially regulated by MEK\/ERK activation","volume":"279","author":"Chang MC","journal-title":"J Biol Chem"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.2004.01038.x"},{"key":"e_1_2_6_15_2","first-page":"189","article-title":"Matrix metalloproteinase\u20102 and \u20109 activities correlates with the disease\u2010free survival of oral squamous cells carcinoma patients","volume":"20","author":"Yorioka CW","year":"2002","journal-title":"Int J Oncol"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgg083"},{"key":"e_1_2_6_17_2","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.oraloncology.2005.01.007","article-title":"Cell\u2010mediated immunity and head and neck cancer: with special emphasis on betel quid chewing habit","volume":"41","author":"Chang MC","journal-title":"Oral Oncol"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2007.01035.x"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1368-8375(01)00045-8"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/jso.20276"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2008.00701.x"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/21.7.1365"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1177\/0192623309356453"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/em.20463"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910520225"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-1218(10)80007-2"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2005.05.044"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2005.07.026"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2011.11.001"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02577-10"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/hed.20561"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2011.10.001"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2007.00552.x"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1067\/moe.2003.121"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0929-6646(10)60129-5"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2008.05.004"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-007-9761-5"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012493808790"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1368-8375(03)00101-5"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.2174\/1566523024605564"}],"container-title":["Head &amp; Neck"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhed.23119","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hed.23119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T11:12:52Z","timestamp":1700651572000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hed.23119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,8,21]]},"references-count":39,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2013,9]]}},"alternative-id":["10.1002\/hed.23119"],"URL":"https:\/\/doi.org\/10.1002\/hed.23119","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718091223.793485151","asserted-by":"object"}]},"ISSN":["1043-3074","1097-0347"],"issn-type":[{"value":"1043-3074","type":"print"},{"value":"1097-0347","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,8,21]]}}}