Curcumin inhibits glycolysis via EP300 in oral squamous cell carcinoma.

Curcumin, a natural polyphenolic compound known for its antitumor efficacy, has been shown to modulate glycolytic pathways in various cancers. However, its specific role and underlying mechanism in oral squamous cell carcinoma (OSCC) remain insufficiently explored. This study systematically investigated the impact of curcumin on glycolysis in OSCC cells, with particular focus on EP300, a key epigenetic regulator, as a target of curcumin’s action. Human oral squamous cell carcinoma cell lines (UM-SCC-1 and HSC-3) and normal human oral keratinocytes (HOK) were treated with curcumin at various concentrations. Cell proliferation, clonogenic ability, and migration were assessed using CCK-8, colony formation, and wound-healing assays, respectively. Glycolytic activity was evaluated by measuring glucose uptake and lactate production. An EP300-overexpressing UM-SCC-1 cell line was established via plasmid transfection. Protein-protein interaction (PPI) network analysis through the STRING database identified potential EP300-regulated glycolytic enzymes. Expression levels of EP300 and key glycolytic markers (PKM2, LDHA, GLUT1) were quantified using qRT-PCR and Western blot. Curcumin significantly inhibited proliferation, clonogenic growth, and migration of OSCC cells (UM-SCC-1 and HSC-3) in a concentration-dependent manner. Curcumin treatment markedly reduced glucose uptake and lactate production in OSCC cells, indicating effective suppression of glycolytic activity. At the molecular level, Curcumin downregulated EP300 expression. EP300 overexpression enhanced glycolytic activity and increased the expression of key glycolytic enzymes, including PKM2, LDHA, and GLUT1, and partially reversed the inhibitory effects of curcumin on glycolysis and enzyme expression. Bioinformatic analysis confirmed interactions between EP300 and these glycolytic enzymes. Curcumin suppresses glycolysis in OSCC by modulating EP300 expression and downregulating key glycolytic enzymes such as PKM2, LDHA, and GLUT1. These findings are consistent with curcumin’s potential role as a metabolic modulator in OSCC.