Berberine Hydrochloride Inhibits the Proliferation and Tumorigenesis of Hepatocellular Carcinoma Cells by Regulating Amino Acid Metabolism

作者：Qipan Jian, Yuhang Shu, Zhenhui Li, Qingjia Chi, Muhammad Nisar, Chunli Wang, Guang‐Zhong Wang, Kang Xu · 发表于：Anti-Cancer Agents in Medicinal Chemistry · 年份：2025 · DOI：10.2174/0118715206357856241223095321 · 被引用次数：1 · 研究领域：Berberine and alkaloids research、Metabolomics and Mass Spectrometry Studies、Cancer Research and Treatments

BACKGROUND: Hepatocellular carcinoma (HCC) is a frequent cancer in the world and a highly fatal primary liver cancer. Berberine hydrochloride (BBH) has exhibited therapeutic potential against HCC with no toxicity and good anti-tumor effects. OBJECTIVE: The objective of this study is to investigate the role of BBH against HCC and elucidate its underlying mechanism. METHODS: In Hep3B and HCCLM3 cell lines, the anti-tumor effects of BBH were assessed using MTT, wound healing, and colony formation assays, which measure cell viability, migration, and proliferation, respectively. Protein expression linked to apoptosis and cell cycle regulation was examined using western blotting. RNA sequencing and metabolomics analysis were performed to identify the metabolic and molecular targets of BBH, which were further confirmed by molecular docking. Furthermore, a tumor model was established by subcutaneous injection of Hep3B cells into nude mice to determine whether BBH has antitumor effects in vivo. RESULTS: Following adose-dependent manner, BBH efficiently reduced the viability, and enhanced migration, inducing cell cycle arrest via downregulation of CDK1 and CCND1. It also induced apoptosis by downregulating BCL2 and upregulating BAX. RNA-seq analysis revealed that BBH-treated cells had differentially expressed genes enriched in amino acid metabolic pathways. Furthermore, metabolomics analysis depicted BBH-mediated inhibition of alanine, methionine, and glutamic acid biosynthesis in HCC ...