Ethyl gallate as a novel ERK1/2 inhibitor suppresses patient‐derived esophageal tumor growth

: Ethyl gallate (EG) is a phenolic compound that is isolated from walnut kernels, euphorbia fischeriana, and galla rhois. It has been reported to exhibit antioxidant and anticancer activities. However, EG's effects on esophageal cancer have not yet been investigated. In the present study, we report that EG is a novel ERK1/2 inhibitor that suppresses esophageal cancer growth in vitro and in vivo. EG suppressed anchorage-dependent and -independent esophageal cancer cell growth. The results of in vitro kinase assays and cell-based assays indicated that EG directly binds to and inhibits ERK1 and ERK2 activities and their downstream signaling. Additionally, EG's inhibitory effect on cell growth is resistant to the re-activation of ERK1/2. EG increased G2/M phase cell cycle by reducing the expression of cyclin A2 and cyclin B1. The compound also stimulated cellular apoptosis through the activation of caspases 3 and 7 and inhibition of BCL2 expression. Notably, EG inhibited patient-derived esophageal tumor growth in an in vivo mouse model. These results indicate that EG is an ERK1/2 inhibitor that could be useful for treating esophageal cancer.