{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:14:48Z","timestamp":1790212488346,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA228404"],"award-info":[{"award-number":["CA228404"]}],"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":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Prostate cancer (PCa) is the second most common cancer and second leading cause of cancer death for American men. Chemoprevention by using phytochemicals offers a promising approach to improve outcomes due to their ability to act on cancer cell metabolism and growth while maintaining low toxicity profiles. The goal of this study was to assess the combination of xanthohumol (XAN) and ursolic acid (UA) given in the diet for synergistic efficacy against PCa progression and identify potential mechanisms of action. PCa cells were treated with the combination to evaluate cell survival and colony formation. Two mouse models of PCa were used to evaluate tolerability and efficacy of dietary administration of the combination and to further understand mechanism(s) of action. The combination of XAN\u2009+\u2009UA reduced PCa cell survival and colony formation. The combination given in the diet significantly and synergistically inhibited growth of HMVP2 PCa allograft tumors and also inhibited PCa progression in HiMyc mice. Mechanistically, inhibition of polyamine synthesis and epithelial\u2010to\u2010mesenchymal transition contributed to the inhibition of HMVP2 allograft tumor growth, while the inhibition of PCa progression in HiMyc mice was associated with activation of the unfolded protein response pathway and apoptosis. Further studies in cultured PCa cells revealed additional effects of the combination on several oncogenic signaling pathways (e.g, phospho\u2010STAT3) and cell cycle regulatory proteins (e.g, cyclin D1, phospho\u2010Rb).<\/jats:p>","DOI":"10.1002\/mc.70087","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T10:02:40Z","timestamp":1770717760000},"page":"508-522","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Combination of Xanthohumol and Ursolic Acid in the Diet Leads to Synergistic Inhibition of Prostate Cancer Progression"],"prefix":"10.1002","volume":"65","author":[{"given":"Rachel","family":"Clark","sequence":"first","affiliation":[{"name":"Division of Pharmacology and Toxicology, College of Pharmacy The University of Texas at Austin Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achinto","family":"Saha","sequence":"additional","affiliation":[{"name":"Division of Pharmacology and Toxicology, College of Pharmacy The University of Texas at Austin Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Lavender Hackman","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences The University of Texas at Austin Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea A.","family":"Friedman","sequence":"additional","affiliation":[{"name":"Division of Pharmacology and Toxicology, College of Pharmacy The University of Texas at Austin Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruggiero","family":"Gorgoglione","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences The University of Texas at Austin Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Tiziani","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences The University of Texas at Austin Austin Texas USA"},{"name":"Dell Medical School, Dell Pediatric Research Institute The University of Texas at Austin Austin Texas USA"},{"name":"Center for Molecular Carcinogenesis and Toxicology The University of Texas at Austin Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"DiGiovanni","sequence":"additional","affiliation":[{"name":"Division of Pharmacology and Toxicology, College of Pharmacy The University of Texas at Austin Austin Texas USA"},{"name":"Dell Medical School, Dell Pediatric Research Institute The University of Texas at Austin Austin Texas USA"},{"name":"Center for Molecular Carcinogenesis and Toxicology The University of Texas at Austin Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"Key Statistics for Prostate Cancer | Prostate Cancer Facts American Cancer Society [Internet] https:\/\/www.cancer.org\/cancer\/types\/prostate-cancer\/about\/key-statistics.html."},{"key":"e_1_2_11_3_1","unstructured":"What Are the Survival Rates for Prostate Cancer? [Internet] https:\/\/www.cancer.org\/cancer\/types\/prostate-cancer\/detection-diagnosis-staging\/survival-rates.html."},{"key":"e_1_2_11_4_1","unstructured":"Chemotherapy for Prostate Cancer [Internet] https:\/\/www.cancer.org\/cancer\/types\/prostate-cancer\/treating\/chemotherapy.html."},{"key":"e_1_2_11_5_1","unstructured":"Active Surveillance for Prostate Cancer Watchful Waiting for Prostate Cancer [Internet] https:\/\/www.cancer.org\/cancer\/types\/prostate-cancer\/treating\/watchful-waiting.html."},{"key":"e_1_2_11_6_1","unstructured":"Hormone Therapy for Prostate Cancer [Internet] https:\/\/www.cancer.org\/cancer\/types\/prostate-cancer\/treating\/hormone-therapy.html."},{"key":"e_1_2_11_7_1","unstructured":"Preventing Cancer [Internet] https:\/\/www.who.int\/activities\/preventing-cancer."},{"key":"e_1_2_11_8_1","unstructured":"Understanding Your Pathology Report: Prostatic Intraepithelial Neoplasia (PIN) and Intraductal Carcinoma [Internet] https:\/\/www.cancer.org\/cancer\/diagnosis-staging\/tests\/biopsy-and-cytology-tests\/understanding-your-pathology-report\/prostate-pathology\/high-grade-prostatic-intraepithelial-neoplasia.html."},{"issue":"4","key":"e_1_2_11_9_1","first-page":"171","article-title":"High\u2010Grade Prostatic Intraepithelial Neoplasia","volume":"6","author":"Bostwick D. 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