{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:59:46Z","timestamp":1790229586352,"version":"4.1.0"},"reference-count":37,"publisher":"Bentham Science Publishers Ltd.","issue":"14","content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["ACAMC"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Hepatocellular carcinoma (HCC) is a frequent cancer in the world and a highly fatal\nprimary liver cancer. Berberine hydrochloride (BBH) has exhibited therapeutic potential against HCC with no\ntoxicity and good anti-tumor effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>The objective of this study is to investigate the role of BBH against HCC and elucidate its underlying\nmechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>In Hep3B and HCCLM3 cell lines, the anti-tumor effects of BBH were assessed using MTT, wound\nhealing, and colony formation assays, which measure cell viability, migration, and proliferation, respectively.\nProtein expression linked to apoptosis and cell cycle regulation was examined using western blotting. RNA sequencing\nand metabolomics analysis were performed to identify the metabolic and molecular targets of BBH,\nwhich were further confirmed by molecular docking. Furthermore, a tumor model was established by subcutaneous\ninjection of Hep3B cells into nude mice to determine whether BBH has antitumor effects in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Following adose-dependent manner, BBH efficiently reduced the viability, and enhanced migration,\ninducing cell cycle arrest via downregulation of CDK1 and CCND1. It also induced apoptosis by downregulating\nBCL2 and upregulating BAX. RNA-seq analysis revealed that BBH-treated cells had differentially expressed\ngenes enriched in amino acid metabolic pathways. Furthermore, metabolomics analysis depicted BBH-mediated\ninhibition of alanine, methionine, and glutamic acid biosynthesis in HCC cells. Protein-protein interaction (PPI)\nnetwork analysis and molecular docking studies have identified DOT1L, SMYD2, and KMT2C as potential molecular\ntargets for BBH. Tumor samples were stained with HE and KI67 immunohistochemistry, and BBH significantly\ninhibited tumor growth in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>BBH may inhibit HCC tumorigenesis by disrupting amino acid metabolism and holds potential as a\ntherapeutic agent for HCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2174\/0118715206357856241223095321","type":"journal-article","created":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T06:46:14Z","timestamp":1760769974000},"page":"1380-1391","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Berberine Hydrochloride Inhibits the Proliferation and Tumorigenesis of Hepatocellular Carcinoma Cells by Regulating Amino Acid Metabolism"],"prefix":"10.2174","volume":"26","author":[{"given":"Qipan","family":"Jian","sequence":"first","affiliation":[{"name":"Hubei Provincial Engineering Technology Research Center for Chinese Medicine Processing, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"Shu","sequence":"additional","affiliation":[{"name":"Hubei Provincial Engineering Technology Research Center for Chinese Medicine Processing, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhui","family":"Li","sequence":"additional","affiliation":[{"name":"Hubei Provincial Engineering Technology Research Center for Chinese Medicine Processing, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingjia","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Engineering Structure and Mechanics, School of Science, Wuhan University of Technology, Wuhan, 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Farrukh","family":"Nisar","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biochemistry, Cholistan University of Veterinary and Animal Sciences (CUVAS), Bahawalpur, 63100, Pakistan"},{"name":"Ministry of Education and Jiangxi Key Laboratory of Crop Physiology, Ecology and Genetic Breeding, Jiangxi Agricultural University, Nanchang, 330045, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunli","family":"Wang","sequence":"additional","affiliation":[{"name":"Hubei Shizhen Laboratory, Wuhan, 430065, China"},{"name":"School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangzhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Hubei Provincial Engineering Technology Research Center for Chinese Medicine Processing, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China"},{"name":"Hubei Shizhen Laboratory, Wuhan, 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Xu","sequence":"additional","affiliation":[{"name":"Hubei Provincial Engineering Technology Research Center for Chinese Medicine Processing, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China"},{"name":"Hubei Shizhen Laboratory, Wuhan, 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"965","reference":[{"key":"ref=1","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1097\/HM9.0000000000000074","volume":"3","author":"Shao Y.","year":"2023","unstructured":"Shao Y.; Drug co-administration in the tumor immune microenvironment of Hepatocellular carcinoma. 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