{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T06:32:13Z","timestamp":1764311533191,"version":"3.46.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with limited therapeutic options and poor prognosis, highlighting the urgent need for novel targets and effective agents. PCID2 (PCI-domain containing protein 2) has recently been recognized as a potential therapeutic target; however, specific inhibitors remain unidentified. Natural products, particularly monomeric compounds derived from traditional Chinese medicine (TCM), provide an important source for novel anticancer candidates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A molecular docking-based virtual screening of TCM-derived compounds were used to identify small molecules targeting PCID2. The binding interaction between the top candidate, 1,2,3,4,6-Penta-O-galloyl-\u03b2-D-glucose (\u03b2-PGG), and PCID2 was validated using surface plasmon resonance (SPR). The cytotoxicity and effects of \u03b2-PGG on HCC cell proliferation, migration, invasion, apoptosis, and cell cycle progression were evaluated\n                      <jats:italic>in vitro<\/jats:italic>\n                      . Exploratory analysis related to mechanisms were performed via Western blotting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\u03b2-PGG was identified as a promising PCID2-targeting compound by molecular docking, and SPR confirmed its direct binding to PCID2. \u03b2-PGG significantly reduced HCC cell proliferation, migration, and invasion, while inducing apoptosis and cell cycle arrest. Treatment with \u03b2-PGG impeded the G0\/G1 or S phase to G2\/M phase. Mechanistically, \u03b2-PGG decreased PCID2 expression and downregulated Cyclin D1 and CDK6. At higher concentrations, \u03b2-PGG also suppressed PI3K and Akt phosphorylation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\u03b2-PGG exhibits potent anti-HCC activity by modulating PCID2 expression, PI3K\/Akt signaling, and cell cycle regulation, and it represents a promising lead compound with PCID2-targeting potential. This study not only support a rationale for further exploration of PCID2 as a therapeutic target in HCC but also provide valuable insights into the discovery of novel lead compounds from TCM for liver cancer treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1687517","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T06:27:54Z","timestamp":1764311274000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A natural PCID2-Targeting compound suppresses hepatocellular carcinoma progression: evidence from structure-based discovery and biological evaluation"],"prefix":"10.3389","volume":"16","author":[{"given":"Zebanuer","family":"Yuemaierjiang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiamin","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaping","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Xi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyi","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1016\/j.bmcl.2016.12.073","article-title":"Inhibition of invasion by N-trans-feruloyloctopamine via AKT, p38MAPK and EMT related signals in hepatocellular carcinoma cells","volume":"27","author":"Bai","year":"2017","journal-title":"Bioorg. 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