Gallic Acid as a Non-cytotoxic Modulator of the ROS–EGFR–ERK–EMT Axis in Xenograft-derived T98G Glioblastoma Cells

BACKGROUND/AIM: microenvironment often display enhanced invasion driven by EGFR-ERK signaling and epithelial-mesenchymal transition (EMT). This study aimed to characterize an EGFR-ERK-dependent T98G subline (T98G-xeno) and to determine how gallic acid (GA) modulates reactive oxygen species (ROS), EGFR-ERK signaling, EMT and migration. MATERIALS AND METHODS: Parental T98G and T98G-xeno cells were compared for proliferation, EMT markers and migration. GA cytotoxicity, ROS, EGFR-ERK signaling and migration were assessed after GA, EGF, N-acetyl-L-cysteine (NAC) or EGFR siRNA treatment. RESULTS: T98G cells. Non-apoptotic GA increased ROS, decreased p-EGFR/EGFR and p-ERK/ERK ratios, restored E-cadherin/ZO-1, reduced N-cadherin/vimentin and inhibited wound closure and migration. EGF-induced EGFR-ERK activation and migration were antagonized by GA. EGFR siRNA mimicked GA, whereas NAC attenuated GA-induced ROS and partially rescued these effects. CONCLUSION: GA targets a ROS-EGFR-ERK-EMT axis in T98G-xeno cells, acting as a non-cytotoxic modulator that reverses EMT and limits migration. These findings suggest that GA-based strategies may help restrain invasion in EGFR-ERK-addicted, EMT-enriched GBM.