{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T20:28:50Z","timestamp":1786566530757,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["2022CFD068"],"award-info":[{"award-number":["2022CFD068"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Hepatocellular carcinoma (HCC) is a leading cause of cancer\u2010related mortality worldwide, which is difficult to control with conventional surgical and chemotherapeutic approaches owing to distant metastasis. Therefore, alternative medicines with high efficacy but minimal side effects are urgently needed. Recently, increasing evidence has demonstrated that ononin, an isoflavone glycoside widely distributed in herbs and food plants, exhibits potent anticancer effects across various cancers. Our research aimed to determine the influence of ononin on HCC growth and metastasis and identify the potential mechanism of action. The anti\u2010proliferative and anti\u2010metastatic properties of ononin in human HCC cells were determined using MTT, colony formation, flow cytometry, wound\u2010healing, and Transwell assays. The expression of cell cycle\u2010related proteins, matrix metalloproteinases (MMP\u20102 and MMP\u20109), and PI3K\/AKT\/mTOR pathway\u2010related molecules in HCC cells was examined by western blotting. TGF\u2010\u03b21 or the PI3K activator 740Y\u2010P was used for combined cell treatment with ononin to validate the effects of ononin on TGF\u2010\u03b21\u2010triggered HCC cell metastasis and the role of the PI3K\/AKT\/mTOR pathway in ononin's anticancer effects. The in vivo therapeutic effects were finally validated in xenograft mouse models. Ononin suppressed HCC cell growth, induced G0\/G1 cell cycle arrest, and reduced CDK6, cyclin D1, and CDK4 protein levels in HCC cells. Ononin inhibited HCC cell migration and invasion and downregulated MMP\u20102\/9 expression with or without TGF\u2010\u03b21 stimulation. Ononin attenuated p\u2010PI3K, p\u2010AKT, and p\u2010mTOR protein levels in HCC cells, and 740Y\u2010P abolished the repression of ononin on HCC cell growth and metastasis. Additionally, ononin restricted tumor growth, decreased Ki67 and p\u2010AKT expression, and curbed lung metastasis in xenograft mouse models. Ononin inhibits HCC growth and metastasis by downregulating MMP\u20102 and MMP\u20109 through inactivating the PI3K\/AKT\/mTOR signaling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbt.70804","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T09:12:22Z","timestamp":1774429942000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ononin Inhibits the Growth and Metastasis of Hepatocellular Carcinoma by Suppressing MMP\u20102 and MMP\u20109 via PI3K\/AKT\/mTOR Signaling"],"prefix":"10.1002","volume":"40","author":[{"given":"Shasha","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University Huangshi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9595-1881","authenticated-orcid":false,"given":"Jun","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University Huangshi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfei","family":"Fu","sequence":"additional","affiliation":[{"name":"Personnel Section Huangshi Maternal and Child Health Hospital Huangshi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.5582\/bst.2022.01061"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.currproblcancer.2017.10.007"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241512224"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01200-4"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11864-023-01098-9"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2020.07.008"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4586"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-022-01347-8"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pmbts.2017.02.005"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-40146-7_5"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23010146"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/9423907"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-023-01827-6"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106553"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874467214666210120152657"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom9120758"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222413659"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.117375"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sjbs.2021.06.031"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.1c00008"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.776"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2022.116179"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.23735"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15030758"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-023-2499-2"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1914937117"},{"key":"e_1_2_10_28_1","doi-asserted-by":"crossref","first-page":"S228","DOI":"10.3350\/cmh.2024.0824","article-title":"Hepatocellular Carcinoma: Updates on Epidemiology, Surveillance, Diagnosis and Treatment","volume":"31","author":"Hwang S. 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