A new epigallocatechin gallate derivative isolated from Anhua dark tea sensitizes the chemosensitivity of gefitinib via the suppression of PI3K/mTOR and epithelial-mesenchymal transition

Abstract The acquired resistance to gefitinib limits its clinical application. Epigallocatechin-3-gallate (EGCG) has been found to enhance the efficacy of gefitinib against resistant. However, the cellular and molecular mechanisms have not been completely illuminated in NSCLC. In this study, a new epigallocatechin gallate derivative (2R,3R-6-methoxycarbonylgallocatechin-3-O-gallate, the following referred to as EGCGD) (1) and three known epigallocatechin gallate compounds including epicatechin-3-O-gallate (2), gallocatechin-3-O-gallate (3) and epigallocatechin-3-O-gallate (4, EGCG) were isolated and identified from Anhua dark tea. The pharmacological studies showed EGCGD was more effective against gefitinib-resistant HCC827-Gef cells compared to that of other three epigallocatechin gallate compounds including EGCG, suggesting that introduction of 6-methoxycarbonyl to EGCG might enhance its antitumor activities. Further study on molecular mechanism showed EGCGD increased the potency of gefitinib against HCC827-Gef cells via suppression of epithelial-Mesenchymal transition (EMT) and dual inhibition of PI3K/mTOR.