{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T12:03:28Z","timestamp":1766664208405,"version":"3.41.2"},"reference-count":68,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T00:00:00Z","timestamp":1579824000000},"content-version":"am","delay-in-days":354,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2019,2,4]],"date-time":"2019-02-04T00:00:00Z","timestamp":1549238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007917","name":"Agricultural Research Service","doi-asserted-by":"publisher","award":["8050\u201051000\u2010096\u201001S)"],"award-info":[{"award-number":["8050\u201051000\u2010096\u201001S)"]}],"id":[{"id":"10.13039\/100007917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:sec><jats:title>Scope<\/jats:title><jats:p>High\u2010fat diets (HFDs) and adiposity increase colorectal cancer risk, in part by elevating pro\u2010inflammatory cytokines that activate pro\u2010cancerous signaling pathways. Curcumin (CUR), a dietary polyphenol and salsalate (SAL), an non\u2010steroidal anti\u2010inflammatory drug (NSAID) lacking the gastrotoxicity of aspirin, each suppress inflammatory signaling, but via different cellular pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>A\/J mice (<jats:italic>n<\/jats:italic>\u00a0=\u00a0110) are fed a low\u2010fat diet (LFD, 10% kcal), a HFD (60% kcal), a HFD containing 0.4% CUR, a HFD containing 0.3% SAL, or a HFD containing both agents (CUR\/SAL). All mice receive six injections of azoxymethane. Compared to LFD\u2010fed mice, HFD\u2010fed mice display elevated colonic cytokines, crypt cell proliferation, and increased tumorigenesis (<jats:italic>p<\/jats:italic> &lt; 0.05). CUR\/SAL significantly reduces colonic cytokines (<jats:italic>p<\/jats:italic> &lt; 0.01), suppresses activation of the PI3K\/Akt\/mTOR\/NF\u2010\u03baB\/<jats:italic>Wnt<\/jats:italic> pathways (<jats:italic>p<\/jats:italic> &lt; 0.01), activates AMPK (<jats:italic>p<\/jats:italic> &lt; 0.01), attenuates abnormal proliferation of the colonic mucosa (<jats:italic>p<\/jats:italic> &lt; 0.05), and reduces tumor multiplicity and burden (<jats:italic>p<\/jats:italic> &lt; 0.05), in comparison to the HFD control. In contrast, CUR or SAL alone does not suppress abnormal crypt cell proliferation or tumor multiplicity, and is largely ineffective in modifying activation of these signaling pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These observations demonstrate the superiority of the CUR\/SAL over the individual agents and provide a scientific basis for future translational studies in obese subjects and\/or those habitually consuming HFDs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.201801097","type":"journal-article","created":{"date-parts":[[2019,1,25]],"date-time":"2019-01-25T02:55:01Z","timestamp":1548384901000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The Combination of Curcumin and Salsalate is Superior to Either Agent Alone in Suppressing Pro\u2010Cancerous Molecular Pathways and Colorectal Tumorigenesis in Obese Mice"],"prefix":"10.1002","volume":"63","author":[{"given":"Xian","family":"Wu","sequence":"first","affiliation":[{"name":"Vitamins &amp; Carcinogenesis Laboratory Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University  Boston MA 02111"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gar Yee","family":"Koh","sequence":"additional","affiliation":[{"name":"Vitamins &amp; Carcinogenesis Laboratory Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University  Boston MA 02111"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yueyi","family":"Huang","sequence":"additional","affiliation":[{"name":"Vitamins &amp; Carcinogenesis Laboratory Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University  Boston MA 02111"},{"name":"Friedman School of Nutrition Science and Policy Tufts University  Boston MA 02111"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jimmy W.","family":"Crott","sequence":"additional","affiliation":[{"name":"Vitamins &amp; Carcinogenesis Laboratory Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University  Boston MA 02111"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roderick T.","family":"Bronson","sequence":"additional","affiliation":[{"name":"Rodent Histopathology Core Harvard Medical School  Boston MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel B.","family":"Mason","sequence":"additional","affiliation":[{"name":"Vitamins &amp; 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