{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:11:36Z","timestamp":1792789896961,"version":"4.5.0"},"reference-count":63,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hunan University of Medicine","award":["2015TP1020-2025-01"],"award-info":[{"award-number":["2015TP1020-2025-01"]}],"id":[{"id":"https:\/\/ror.org\/05htk5m33","id-type":"ROR","asserted-by":"crossref"}]},{"award":["2015TP1020-2025-01"],"award-info":[{"award-number":["2015TP1020-2025-01"]}],"id":[{"id":"https:\/\/ror.org\/047sgsy47","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) is the most common primary liver cancer and remains a major cause of cancer-related death worldwide. Corosolic acid (CA), an ursane-type pentacyclic triterpenoid with antidiabetic, anti-inflammatory, and antitumour activities, has attracted interest as a potential natural compound for HCC treatment. This review critically evaluates CA as a molecular lead for HCC by integrating its physicochemical characteristics with direct preclinical evidence, cross-model hypotheses, and development constraints. Current studies indicate that CA suppresses HCC cell proliferation and migration, disrupts cell-cycle progression, and promotes cell death, with antitumour effects also observed in animal models. These activities have been associated with mitochondrial apoptosis and endoplasmic reticulum stress, Yes-associated protein (YAP)-related growth regulation, increased susceptibility to ferroptosis, and inhibition of vascular endothelial growth factor receptor 2 (VEGFR2)-related migratory signalling. Interestingly, evidence from other tumour, metabolic, inflammatory, and fibrotic models further suggests that CA may influence tumour metabolism, autophagy, the immunosuppressive microenvironment, fibrosis, and angiogenesis. However, these cross-model findings require direct validation in HCC. Although CA shows promising preclinical activity, it should be regarded as a natural lead compound rather than an established HCC therapy. Major unresolved gaps include poorly defined dose\u2013exposure\u2013response relationships, limited validation of the principal mechanisms in clinically relevant HCC models, and insufficient evidence that optimised formulations or combination regimens improve efficacy without increasing toxicity.<\/jats:p>","DOI":"10.3390\/molecules31193474","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:10:54Z","timestamp":1790673054000},"page":"3474","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Corosolic Acid in Hepatocellular Carcinoma: Molecular Properties, Evidence Boundaries, and Development Priorities"],"prefix":"10.3390","volume":"31","author":[{"given":"Shiyi","family":"Zhu","sequence":"first","affiliation":[{"name":"Hengyang Medical College, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoping","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate School, Youjiang Medical University for Nationalities, Baise 533000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarui","family":"Qu","sequence":"additional","affiliation":[{"name":"Hengyang Medical College, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0876-2205","authenticated-orcid":false,"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaiqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Dong Medicine, Hunan University of Medicine, Huaihua 418000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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