20(S)-Ginsenoside Rh2 targets the SUCLG2/p300/H3K18la axis to regulate histone lactylation and inhibit the proliferation of glioma cells
Glioma is a common and malignant brain tumor, and its proliferative properties make treatment highly challenging. This study aims to explore the inhibitory effect of 20(S)-Ginsenoside Rh2 (GIN) on glioma and elucidateit the deeply molecular mechanisms. Various experimental methods, including MTT assay, Edu staning, flow cytometry, RNA sequencing, Metabolite Extraction and Gas Chromatography Mass Spectrometric (GC-MS), and western blotting, molecular docking was used to systematically evaluate the effects of GIN on U87 and LN229 glioma cells in vitro. The tumor xenograft assay was used to evaluate the anti-glioma effects of GIN in vivo. Results showed that GIN significantly inhibited glioma cell viability in a dose-dependent manner and induced cell cycle arrest in the G1 phase by down-regulating the expression of Cyclin D1, Cyclin E1, and CDK2. Furthermore, GIN affected the cellular metabolism by regulating glycolysis metabolic pathway, which further inhibited the H3 histone lactylation levels. IP experiments further demonstrated that GIN selectively reduced lactylation levels at histone H3K9 and H3K18 sites by affecting the interaction between SUCLG2 and p300 proteins, thereby regulating the proliferation of glioma cells. In conclusion, GIN showed a good anti-tumor effect by targeting the SUCLG2/p300/H3K18la axis, suggesting that GIN has a potential to be used as a novel anti-glioma drug.