Skullcapflavone II Inhibits SLC1A4-Mediated L-Serine Uptake and Promotes Mitochondrial Damage in Gastric Cancer.

ABSTRACT: Gastric cancer (GC) is one of the most lethal human malignancies worldwide. Serine metabolism is essential for meeting biosynthetic demands and regulating the redox state of GC cells. This study demonstrates that Skullcapflavone II (SkII) selectively inhibits the proliferation and metastasis of GC cells. Transcriptomic and metabolomic analyses reveal that SkII treatment significantly affects serine metabolism in GC cells, and isotope tracing experiments confirmed that SkII reduces intracellular L-serine levels by inhibiting uptake rather than de novo synthesis. Furthermore, IHC analysis reveal significant upregulation of the L-serine transporter SLC1A4 in GC tissues. Binding studies using PELSA, SPR, DARTS, CETSA, and MD suggest that SLC1A4 is a potential direct target of SkII. SkII-induce

SUBMITTER: Zhao J 

PROVIDER: S-EPMC12677694 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature