Ginsenoside Rg3 exerts anticancer effects in lung cancer through metabolite Histon H3

Objectives: To investigate the effects of ginsenoside Rg3 on metabolites in lung cancer cells. Methods: A549 cells were inoculated into nude BALB/c mice. Ginsenoside Rg3 (0.2 mL) or normal saline was orally administered daily for 12 days. LC/MS-based metabolomics was performed to analyze the metabolite profiles across three groups. Results: In serum samples, 143 metabolites were significantly different between the model and ginsenoside Rg3 groups. In fecal samples, 44 metabolites differed significantly between the two groups. Levels of Lamin A/C and Histon H3 were upregulated in model tissues. Ginsenoside Rg3 treatment significantly inhibited the expression of Lamin A/C and Histon H3, suggesting inhibition of histidine metabolism activation in lung cancer. Furthermore, ginsenoside Rg3 or Lamin A knockdown inhibited histamine-induced proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in lung cancer cells. Conclusions: Ginsenoside Rg3 significantly altered the metabolic profile in lung cancer mice. Mechanistically, ginsenoside Rg3 downregulated Lamin A/C through histidine metabolic pathway and suppressed histamine-induced progression of lung cancer.