{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:36:58Z","timestamp":1790519818983,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,11,14]],"date-time":"2013-11-14T00:00:00Z","timestamp":1384387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NCI R01","award":["CA91883"],"award-info":[{"award-number":["CA91883"]}]},{"name":"NCI R01","award":["CA140368"],"award-info":[{"award-number":["CA140368"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Preventive measures against oral carcinogenesis are urgently warranted to lower the high morbidity and mortality associated with this malignancy worldwide. Here, we investigated the chemopreventive efficacy of grape seed extract (GSE) and resveratrol (Res) in 4\u2010nitroquinoline\u20101\u2010oxide (4NQO)\u2010induced tongue tumorigenesis in C57BL\/6 mice. Following 8 weeks of 4NQO exposure (100\u2009\u00b5g\/ml in drinking water), mice were fed with either control AIN\u201076A diet or diet containing 0.2% GSE (w\/w) or 0.25% Res (w\/w) for 8 subsequent weeks, while continued on 4NQO. Upon termination of the study at 16 weeks, tongue tissues were histologically evaluated for hyperplasia, dysplasia, and papillary lesions, and then analyzed for molecular targets by immunohistochemistry. GSE and Res feeding for 8 weeks, moderately decreased the incidence, but significantly prevented the multiplicity and severity of 4NQO\u2010induced preneoplastic and neoplastic lesions, without any apparent toxicity. In tongue tissues, both 4NQO\u2009+\u2009GSE and 4NQO\u2009+\u2009Res treatment correlated with a decreased proliferation (BrdU labeling index) but increased apoptotic death (TUNEL\u2010positive cells) as compared to the 4NQO group. Furthermore, tongue tissues from both the 4NQO\u2009+\u2009GSE and 4NQO\u2009+\u2009Res groups showed an increase in activated metabolic regulator phospho\u2010AMPK (Thr172) and decreased autophagy flux marker p62. Together, these findings suggest that GSE and Res could effectively prevent 4NQO\u2010induced oral tumorigenesis through modulating AMPK activation, and thereby, inhibiting proliferation and inducing apoptosis and autophagy, as mechanisms of their efficacy. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mc.22099","type":"journal-article","created":{"date-parts":[[2013,11,14]],"date-time":"2013-11-14T21:32:05Z","timestamp":1384464725000},"page":"291-300","source":"Crossref","is-referenced-by-count":39,"title":["Grape seed extract and resveratrol prevent 4\u2010nitroquinoline 1\u2010oxide induced oral tumorigenesis in mice by modulating AMPK activation and associated biological responses"],"prefix":"10.1002","volume":"54","author":[{"given":"Sangeeta","family":"Shrotriya","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences Skaggs School of Pharmacy and Pharmaceutical Sciences University of Colorado Denver Anschutz Medical Campus 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