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

Feifei Liu, Xueyin Zu, Xiaomeng Xie, Kangdong Liu, Hanyong Chen, Ting Wang, Fangfang Liu, Ann M. Bode, Yan Zheng, Zigang Dong, Dong Joon Kim

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)533-543
Number of pages11
JournalMolecular Carcinogenesis
Volume58
Issue number4
DOIs
StatePublished - Apr 2019

Bibliographical note

Funding Information:
This work was supported by Key program of Henan Province, China Grant No. 161100510300 and National Natural Science Foundation, China, Grant No. 81572812.

Funding Information:
This work was supported by Key program of Henan Province, China Grant No. 161100510300 and National Natural Science Foundation, China, Grant No. 81572812. FL performed the in vitro experiments and assisted with the cell-based and in vivo experiments. XZ and XX assisted with the cell-based assays. YZ assisted with the in vivo experiments. XZ, TW, and FL performed the in vivo experiments. HC performed the computer modeling. KL and AMB supervised the in vivo experimental design, data analysis, and manuscript editing. ZD supervised the overall experimental design and data analysis. DJK supervised designed experiments, provided the idea, and prepared the manuscript.

Funding Information:
Key program of Henan Province, China, Grant number: 161100510300; National Natural Science Foundation, China, Grant number: 81572812

Publisher Copyright:
© 2018 Wiley Periodicals, Inc.

Keywords

  • ERK1/2
  • esophageal cancer
  • ethyl gallate
  • patient-derived xenograft

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