Therapeutic potential of green tea’s epigallocatechin-3-gallate in oral cancer: a comprehensive systematic review of cellular and molecular pathways

Epigallocatechin-3-gallate (EGCG) has gained attention for its antioxidant, anti-inflammatory, anti-fibrotic, and anti-cancer properties. This review explores the mechanisms by which EGCG influences cellular processes in oral cancer (OC) cells. A systematic search of PubMed, Scopus, and Cochrane databases was conducted to identify evidence-based studies on EGCG's anticancer effects. The risk of bias was assessed using the Cochrane Collaboration's Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I) tool. Thirteen studies (7 in vitro, 5 in vitro with animal models, and 1 clinical study) were included in this review, employing various OC cell lines such as HSC-3, SCC, CAL-27, and KB, along with Tu212 and Tu686 in two investigations. EGCG treatment was reported to inhibit cell proliferation (IC50: 20-80 µM), induced apoptosis (increases of up to 65% in caspase-3 and caspase-7 activity), and reduced migration and invasion by 40-70% across studies. The findings revealed that EGCG demonstrated inhibitory effects on cancer cell growth in Oral Squamous Cell Carcinoma (OSCC) models. Its anticancer effects are mediated through the regulation of Reactive Oxygen Species (ROS) production, suppression of nuclear factor-κB (NF-κB), modulation of mitogen-activated protein kinase pathways, and regulation of epigenetic changes. Combination therapy with cisplatin or resveratrol demonstrated synergistic effects, enhancing cytotoxicity by 30-50% and reducing chemoresistance in vitro and in vivo. Although preclinical evidence is promising, heterogeneity in methodologies and the scarcity of clinical trials limit direct translation. EGCG should therefore be considered an experimental adjunctive strategy for OSCC, with its therapeutic relevance requiring validation in well-designed human studies.