{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T14:40:54Z","timestamp":1771339254336,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2011,5,17]],"date-time":"2011-05-17T00:00:00Z","timestamp":1305590400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Safrole is one of important food\u2010borne phytotoxin that exhibits in many natural products such as oil of sassafras and spices such as anise, basil, nutmeg, and pepper. This study was performed to elucidate safrole\u2010induced apoptosis in human tongue squamous carcinoma SCC\u20104 cells. The effect of safrole on apoptosis was measured by flow cytometry and DAPI staining and its regulatory molecules were studied by Western blotting analysis. Safrole\u2010induced apoptosis was accompanied with up\u2010regulation of the protein expression of Bax and Bid and down\u2010regulation of the protein levels of Bcl\u20102 (up\u2010regulation of the ratio of Bax\/Bcl\u20102), resulting in cytochrome <jats:italic>c<\/jats:italic> release, promoted Apaf\u20101 level and sequential activation of caspase\u20109 and caspase\u20103 in a time\u2010dependent manner. We also used real\u2010time PCR to show safrole promoted the mRNA expressions of caspase\u20103, \u20108, and \u20109 in SCC\u20104 cells. These findings indicate that safrole has a cytotoxic effect in human tongue squamous carcinoma SCC\u20104 cells by inducing apoptosis. The induction of apoptosis of SCC\u20104 cells by safrole is involved in mitochondria\u2010 and caspase\u2010dependent signal pathways. \u00a9 2011 Wiley Periodicals, Inc. Environ Toxicol, 2012.<\/jats:p>","DOI":"10.1002\/tox.20658","type":"journal-article","created":{"date-parts":[[2011,5,17]],"date-time":"2011-05-17T14:15:33Z","timestamp":1305641733000},"page":"433-444","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Safrole induces cell death in human tongue squamous cancer SCC\u20104 cells through mitochondria\u2010dependent caspase activation cascade apoptotic signaling pathways"],"prefix":"10.1002","volume":"27","author":[{"given":"Fu\u2010Shun","family":"Yu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"An\u2010Cheng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jai\u2010Sing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun\u2010Shu","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi\u2010Cheng","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u2010Hua","family":"Chiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang\u2010Fang","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing\u2010Gung","family":"Chung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,5,17]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5381.1322"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx00039a024"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4274(01)00370-8"},{"key":"e_1_2_5_5_1","first-page":"67","article-title":"Clomiphene,an ovulation\u2010inducing agent, causes [Ca2+]i increases in human osteoblast\u2010like cells","volume":"44","author":"Chen YC","year":"2001","journal-title":"Chin J Physiol"},{"key":"e_1_2_5_6_1","first-page":"1113","article-title":"Emodin,aloe\u2010emodin and rhein inhibit migration and invasion in human tongue cancer SCC\u20104 cells through the inhibition of gene expression of matrix metalloproteinase\u20109","volume":"36","author":"Chen YY","year":"2010","journal-title":"Int J Oncol"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyq057"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc883"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207102"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737140.8.5.799"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.15.1899"},{"key":"e_1_2_5_12_1","first-page":"4063","article-title":"Berberine induced apoptosis via promoting the expression of caspase\u20108, \u20109 and \u20103, apoptosis\u2010inducing factor and endonuclease G in SCC\u20104 human tongue squamous carcinoma cancer cells","volume":"29","author":"Ho YT","year":"2009","journal-title":"Anticancer Res"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-005-1086-y"},{"key":"e_1_2_5_14_1","first-page":"1","volume-title":"IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. 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