{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:00:40Z","timestamp":1792202440488,"version":"4.4.0"},"reference-count":66,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2019,9,26]],"date-time":"2019-09-26T00:00:00Z","timestamp":1569456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Abnormally upregulated cholesterol and lipid metabolism, observed commonly in multiple cancer types, contributes to cancer development and progression through the activation of oncogenic growth signaling pathways. Although accumulating evidence has shown the preventive and therapeutic benefits of cholesterol-lowering drugs for cancer management, the development of cholesterol-lowering drugs is needed for treatment of cancer as well as metabolism-related chronic diseases. Ursolic acid (UA), a natural pentacyclic terpenoid, suppresses cancer growth and metastasis, but the precise underlying molecular mechanism for its anti-cancer effects is poorly understood. Here, using sterol regulatory element (SRE)-luciferase assay-based screening on a library of 502 natural compounds, this study found that UA activates sterol regulatory element-binding protein 2 (SREBP2). The expression of cholesterol biosynthesis-related genes and enzymes increased in UA-treated hepatocellular carcinoma (HCC) cells. The UA increased cell cycle arrest and apoptotic death in HCC cells and reduced the activation of oncogenic growth signaling factors, all of which was significantly reversed by cholesterol supplementation. As cholesterol supplementation successfully reversed UA-induced attenuation of growth in HCC cells, it indicated that UA suppresses HCC cells growth through its cholesterol-lowering effect. Overall, these results suggested that UA is a promising cholesterol-lowering nutraceutical for the prevention and treatment of patients with HCC and cholesterol-related chronic diseases.<\/jats:p>","DOI":"10.3390\/ijms20194767","type":"journal-article","created":{"date-parts":[[2019,9,27]],"date-time":"2019-09-27T03:03:15Z","timestamp":1569553395000},"page":"4767","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Ursolic Acid Suppresses Cholesterol Biosynthesis and Exerts Anti-Cancer Effects in Hepatocellular Carcinoma Cells"],"prefix":"10.3390","volume":"20","author":[{"given":"Geon-Hee","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Applied Life Science, Graduate School of Konkuk University, College of Biomedical &amp; Health Science, Konkuk University, Chungju 27478, Korea"},{"name":"Diabetes and Bio-Research Center, Konkuk University, Chungju 27478, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Yeon","family":"Kan","sequence":"additional","affiliation":[{"name":"Department of Applied Life Science, Graduate School of Konkuk University, College of Biomedical &amp; Health Science, Konkuk University, Chungju 27478, Korea"},{"name":"Diabetes and Bio-Research Center, Konkuk University, Chungju 27478, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeji","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Applied Life Science, Graduate School of Konkuk University, College of Biomedical &amp; Health Science, Konkuk University, Chungju 27478, Korea"},{"name":"Diabetes and Bio-Research Center, Konkuk University, Chungju 27478, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Applied Life Science, Graduate School of Konkuk University, College of Biomedical &amp; Health Science, Konkuk University, Chungju 27478, Korea"},{"name":"Diabetes and Bio-Research Center, Konkuk University, Chungju 27478, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3638-1488","authenticated-orcid":false,"given":"Hyun Myung","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Life Science, College of Science and Technology, Woosuk University, 66 Daehak-ro, Jincheon-eup, Chungcheongbuk-do 27841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Hyung","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Hong","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Applied Life Science, Graduate School of Konkuk University, College of Biomedical &amp; Health Science, Konkuk University, Chungju 27478, Korea"},{"name":"Diabetes and Bio-Research Center, Konkuk University, Chungju 27478, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kim, Y.S., Lee, Y.M., Oh, T.I., Shin, D.H., Kim, G.H., Kan, S.Y., Kang, H., Kim, J.H., Kim, B.M., and Yim, W.J. 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