Corilagin induces apoptosis in glioblastoma cells by disrupting metabolic homeostasis: a metabolomics perspective

Abstract

Glioblastoma (GBM) is a highly aggressive brain tumor with limited therapeutic potions. Corilagin, a natural polyphenol, exhibits anti-tumor activity, but its systemic metabolic mechanisms in GBM remain uncharacterized. We treated human glioblastoma LN229 and T98G cells with corilagin and evaluated its effects on cell viability, apoptosis, and migration. An untargeted liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approach was performed to comprehensively profile global metabolic alterations in LN229 cells, followed by multivariate statistical analysis and KEGG pathway enrichment. Corilagin significantly inhibited proliferation, induced apoptotic cell death, and suppressed cell migration in a dose-dependent manner in LN229 and T98G cells. Moreover, principal component analysis and partial least squares-discriminate analysis clearly demonstrated that corilagin disrupted the cell metabolic profiles. Forty differential metabolites in LN229 cells responsible for the intervention effect of corilagin were screened and annotated. These metabolites corresponded to thirteen metabolic pathways. Integrated pathway analysis identified profound disruptions in nucleotide metabolism (notably purine and pyrimidine depletion), glycerophospholipid homeostasis (reduced phosphatidylcholine and phosphatidylethanolamine species), and the TCA cycle. The multi-pathway metabolic collapse was associated with the induction of apoptosis. Our study demonstrates that corilagin exerts its potent anti-glioma effects by inducing a coordinated disruption of core metabolic networks essential for GBM cell survival. These findings establish a strong association between corilagin-induced metabolic reprogramming and apoptotic cell death, highlighting its promise as a therapeutic agent targeting the metabolic vulnerabilities of glioblastoma.