{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:11:34Z","timestamp":1790115094817,"version":"4.0.1"},"reference-count":27,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,6,9]],"date-time":"2018-06-09T00:00:00Z","timestamp":1528502400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA054174"],"award-info":[{"award-number":["CA054174"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008635","name":"University of Texas Health Science Center at San Antonio","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008635","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Thymol is a transient receptor potential ankyrin subtype 1 channel, (<jats:styled-content style=\"fixed-case\">TRPA<\/jats:styled-content>1) agonist found in thyme and oregano. Thymol has antioxidant, anti\u2010inflammatory, and antimicrobial properties; thus, thymol is added to many commercially available products including Listerine mouthwash. Thymol is also cytotoxic to <jats:styled-content style=\"fixed-case\">HL<\/jats:styled-content>\u201060 (acute promyelocytic leukemia) cells in vitro. Therefore, we evaluated the effects of thymol against oral squamous cell carcinoma (<jats:styled-content style=\"fixed-case\">OSCC<\/jats:styled-content>) and its anticancer mechanism\u2010of\u2010action.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The antiproliferative effects of thymol in <jats:styled-content style=\"fixed-case\">OSCC<\/jats:styled-content> Cal27 cells were determined by <jats:styled-content style=\"fixed-case\">MTS<\/jats:styled-content> assays. Antitumor effects were evaluated in Cal27\u2010 and HeLa\u2010derived mouse xenografts. Calcium imaging, mitochondrial transmembrane potential (\u0394\u03a8m) studies, and Western blot analysis of cleaved <jats:styled-content style=\"fixed-case\">PARP<\/jats:styled-content> (c\u2010<jats:styled-content style=\"fixed-case\">PARP<\/jats:styled-content>) evaluated thymol's mechanism\u2010of\u2010action.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thymol had significant, long\u2010lasting antiproliferative effects in vitro. In vivo, thymol displayed significant antitumor effects in Cal27\u2010derived tumors. Thymol's anticancer effects were confirmed in HeLa\u2010derived xenografts demonstrating that thymol effects are not tumor\u2010type specific. Calcium imaging verified calcium influx in Cal27 cells that were reversed with the <jats:styled-content style=\"fixed-case\">TRPA<\/jats:styled-content>1 antagonist, <jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content>030031. However, no calcium influx was seen in HeLa cells indicating that <jats:styled-content style=\"fixed-case\">TRP<\/jats:styled-content> channels do not regulate thymol cytotoxicity. This was confirmed using cell viability assays in which pre\u2010treatment with <jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content>030031 had no effect on thymol cytotoxicity. Instead, \u0394\u03a8m studies revealed that thymol induces significant \u0394\u03a8m depolarization and apoptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings provide the first evidence of thymol's novel antitumor effects against <jats:styled-content style=\"fixed-case\">OSCC<\/jats:styled-content> in vivo, which do not rely on <jats:styled-content style=\"fixed-case\">TRPA<\/jats:styled-content>1 activity. Instead, we show that thymol induces mitochondrial dysfunction and apoptosis and may be efficacious against multiple cancers.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jop.12735","type":"journal-article","created":{"date-parts":[[2018,5,19]],"date-time":"2018-05-19T20:39:06Z","timestamp":1526762346000},"page":"674-682","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["Thymol inhibits oral squamous cell carcinoma growth via mitochondria\u2010mediated apoptosis"],"prefix":"10.1111","volume":"47","author":[{"given":"Jorge J.","family":"De La Chapa","sequence":"first","affiliation":[{"name":"Department of Comprehensive Dentistry University of Texas Health Science Center at San Antonio School of Dentistry San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prajjal Kanti","family":"Singha","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Texas Health Science Center at San Antonio School of Medicine San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie R.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Comprehensive Dentistry University of Texas Health Science Center at San Antonio School of Dentistry San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1739-4574","authenticated-orcid":false,"given":"Cara B.","family":"Gonzales","sequence":"additional","affiliation":[{"name":"Department of Comprehensive Dentistry University of Texas Health Science Center at San Antonio School of Dentistry San Antonio TX USA"},{"name":"Cancer Therapy &amp; Research Center University of Texas Health Science Center at San Antonio San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,9]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"Cancer Facts and Figures: Vol.: American Cancer Society 2015.https:\/\/www.cancer.org\/research\/cancer-facts-statistics\/all-cancer-facts-figures\/cancer-facts-figures-2016.htmlAccessed on 11\u201013\u201017."},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.29.2056"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3841.2011.02109.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1271\/bbb.90937"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/09637480701777944"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-009-1429-6"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-010-1050-8"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000331864"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1472-765X.1999.00605.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2008.12.026"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm100062h"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjp.2008.85"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2012.03.055"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2013.12.023"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000101693"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2007.05.006"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2005.04.010"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.08.042"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2011.08.017"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2011.05.009"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm401986p"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2016.05.007"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2342-8-16"},{"key":"e_1_2_7_25_1","first-page":"1557","article-title":"Erdogan, A A comparative study of the antioxidant\/prooxidant effects of carvacrol and thymol at various concentrations on membrane and DNA of parental and drug resistant H1299 cells","volume":"7","author":"Ozkan A","year":"2013","journal-title":"Nat Prod Commun"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.2144\/000113610"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-0711-10-23"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf204525b"}],"container-title":["Journal of Oral Pathology &amp; 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