Epigallocatechin Gallate Attenuates Arecoline-induced Migration and Invasion in Esophageal Squamous Cell Carcinoma Cells Associated With EGFR/AKT/P38 Signaling

<h3>Background/Aim:</h3> Arecoline, the primary alkaloid in areca nut, is a major risk factor for metastasis-associated progression in esophageal squamous cell carcinoma (ESCC). Epigallocatechin gallate (EGCG), a major polyphenol in green tea, has exhibited anti-cancer and anti-metastatic activity in multiple tumor models. However, the effects of EGCG on arecoline-induced metastatic behavior in ESCC have not been directly examined. <h3>Materials and Methods:</h3> In this study, we examined the effects of EGCG on arecoline-induced migration and invasion in human ESCC cells. Parental CE81T/VGH cells and a highly invasive subline, CE81T-M4, were treated with arecoline, EGCG, or their combination. Cell migration and invasion were assessed using the wound-healing and transwell assays, while changes in EGFR-related signaling and epithelial-mesenchymal transition (EMT)-associated markers were analyzed by western blotting and immunofluorescence. <h3>Results:</h3> Arecoline increased ESCC cell motility and invasion and activated EGFR-dependent signaling, including AKT and P38 phosphorylation, accompanied by increased expression of EMT-associated markers. EGCG suppressed these effects in both parental and invasive ESCC cells. Genetic knockdown of <i>AKT</i> reduced P38 activation and VIMENTIN expression, supporting a role for AKT upstream of P38 in regulating EMT-related responses. <h3>Conclusion:</h3> The attenuation of arecoline-driven metastatic behavior in ESCC cells by EGCG is associated with alterations in EGFR-AKT-P38 signaling, supporting its potential role as a dietary or adjunctive agent in areca-associated esophageal cancer.