Cirsiliol suppresses malignant progression of hepatocellular carcinoma via regulation of glutamine metabolism.

BACKGROUND: To investigate the therapeutic potential of cirsiliol in hepatocellular carcinoma (HCC), focusing on its impact on glutamine metabolism. METHODS: HCC cell lines HCCLM3 and Huh7 were treated with cirsiliol, and cell viability and proliferation were assessed using CCK-8 assay. Intracellular concentrations of glutamine, α-ketoglutaric acid (α-KG), and adenosine triphosphate (ATP) were measured to evaluate glutamine metabolism. A xenograft tumor model was employed to examine the in vivo effects of cirsiliol. Additionally, network pharmacological analysis was used to identify potential targets of cirsiliol in HCC. Western blotting was conducted to analyze the modulation of the PI3K/AKT signaling pathway by cirsiliol. RESULTS: Cirsiliol significantly inhibited HCC cell growth both in vitro and in vivo while reducing levels of glutamine, α-KG, and ATP, indicating suppression of glutamine metabolism. Activation of the PI3K signaling pathway reversed the inhibitory effects of cirsiliol on HCC cell growth and metabolism. CONCLUSION: Cirsiliol suppresses glutamine metabolism and inhibits the growth of HCC cells by modulating the PI3K/AKT signaling pathway.