Berberine hydrochloride inhibits the proliferation and tumorigenesis of hepatocellular carcinoma cells by regulating amino acid metabolism

aims: This study aimed to evaluate the therapeutic potential of BBH against HCC cells and explore its effects on tumor cell metabolism background: Hepatocellular carcinoma (HCC) is a highly lethal primary liver cancer and one of the most common malignancies worldwide. Berberine hydrochloride (BBH) has exhibited therapeutic potential against HCC. objective: This study aimed to investigate the role of BBH against HCC and elucidate its underlying mechanism. method: The anti-tumor effects of BBH were evaluated in Hep3B and HCCLM3 cell lines using MTT, wound healing, and colony formation assays to assess cell viability, migration, and proliferation respectively. Western blotting was performed to analyze the expression of proteins associated with cell cycle regulation and apoptosis. RNA sequencing and metabolomics analysis were performed to identify the metabolic and molecular targets of BBH, which were further confirmed by molecular docking. Furthermore, an in vivo subcutaneous tumor model was established in nude mice to validate the anti-carcinogenic effect of BBH. result: BBH effectively decreased the viability, proliferation, and migration of HCC cells in a dose-dependent manner, 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 showed that BBH inhibited the biosynthesis of alanine, methionine, and glutamic acid in the HCC cells. protein-protein interaction (PPI) network analysis and molecular docking identifiedDOT1L, SMYD2, and KMT2C as potential molecular targets for BBH. In vivo, BBH significantly inhibited tumor growth. conclusion: BBH may inhibit HCC tumorigenesis by disrupting amino acid metabolism and holds potential as a therapeutic agent for HCC. other: N/A