LAUSR

Abstract Capsaicin, a kind of alkaloid from pepper cortex, has extensive anti-tumor activities. However, the anti-metastasis effects and mechanisms of capsaicin against hepatocellular carcinoma (HCC) have not been deeply studied so far. In the present work, the anti-metastasis effects of capsaicin were investigated in human hepatoma SMMC-7721 and HepG2 cells, and its mechanisms were explored using metabolomics-based approach. The results showed that capsaicin remarkably suppressed cell proliferation, migration, and invasion, and hampered cell-matrix adhesion in SMMC-7721 and HepG2 cells. Metabolomics approach revealed that 18 differential metabolites, and 5 metabolic pathways including glutathione metabolism, pyruvate metabolism, phenylalanine metabolism, glycine, serine and threonine metabolism, glycerophospholipid metabolism were implicated in the anti-HCC effects of capsaicin. A multi-level network further uncovered the possible molecular mechanisms of capsaicin in regulating these metabolites and metabolic pathways. This study revealed that metabolomics integrating with network-based approach can facilitate understanding of the anti-metastasis mechanisms of capsaicin against HCC.