{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:24:51Z","timestamp":1760217891565,"version":"3.40.5"},"reference-count":48,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,9,19]],"date-time":"2018-09-19T00:00:00Z","timestamp":1537315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 CA54174","R01 CA164159"],"award-info":[{"award-number":["P30 CA54174","R01 CA164159"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:sec><jats:label\/><jats:p>The phytonutrient ursolic acid (UA), present in apples, rosemary, and other plant sources, has anti\u2010cancer properties in a number of systems, including skin cancers. However, few reports have examined upstream mechanisms by which UA may prevent or treat cancer. Recent reports have indicated UA induces death of cancer cell lines via AMP\u2010activated protein kinase (AMPK), an energy\u2010sensing kinase which possesses both pro\u2010metabolic and anti\u2010cancer effects. Other studies have shown UA activates peroxisome proliferator activated receptor \u03b1 (PPAR\u03b1) and the glucocorticoid receptor (GR). Here, we found the cytotoxic effect of UA in skin carcinoma cells required AMPK activation. In addition, two inhibitors of PPAR\u03b1 partially reversed the cytotoxic effects of UA, suggesting its effects are at least partially mediated through this receptor. Finally, inhibition of the GR did not reverse the effects of UA nor did this compound bind the GR under the conditions of experiments performed. Overall, studies elucidating the anti\u2010cancer effects of UA may allow for the development of more potent analogues utilizing similar mechanisms. These studies may also reveal the mediators of any possible side effects or resistance mechanisms to UA therapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mc.22890","type":"journal-article","created":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T15:47:44Z","timestamp":1534952864000},"page":"1698-1706","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Role of AMPK and PPAR\u03b1 in the anti\u2010skin cancer effects of ursolic acid"],"prefix":"10.1002","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2435-7739","authenticated-orcid":false,"given":"Jacob J.","family":"Junco","sequence":"first","affiliation":[{"name":"Department of Pharmacology The University of Texas Health Science Center at San Antonio San Antonio Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiyoon","family":"Cho","sequence":"additional","affiliation":[{"name":"College of Pharmacy The University of Texas at 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