Mechanism of the inhibition of the STAT3 signaling pathway by EGCG

Wang,Yang; Ren,Xuequn; Deng,Chaoyang; Yang,Lu; Yan,Erfu; Guo,Tao; Li,Yanmin; Xu,Marvin Xuejun

doi:10.3892/or.2013.2743

Mechanism of the inhibition of the STAT3 signaling pathway by EGCG

Authors:
- Yang Wang
- Xuequn Ren
- Chaoyang Deng
- Lu Yang
- Erfu Yan
- Tao Guo
- Yanmin Li
- Marvin Xuejun Xu
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Affiliations: Huaihe Hospital, Henan University, Kaifeng 475000, P.R. China, Shanghai McAry Biomedical Technology Co. Ltd., Zhangjiang Hi-Tech Park, Pudong New Area, Shanghai 201203, P.R. China, Department of Pharmacy, Tianjin University, Tianjin, P.R. China, Center for Drug Delivery System, Shanghai Institute of Materia Medica, State Key Laboratory of Drug Research, Chinese Academy of Sciences, Shanghai 201203, P.R. China, Department of Physics, Shangqiu Normal College, Shangqiu 476000, P.R. China, Department of Pharmacology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
Published online on: September 20, 2013 https://doi.org/10.3892/or.2013.2743
Pages: 2691-2696

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Abstract

Signal transducer and activator of transcription 3 (STAT3) is an oncogene that promotes cell survival, proliferation, and motility. In the present study, we explored the mechanism involved in the inhibition by epigallocatechin-3-gallate (EGCG) of STAT3 signaling as detected by surface plasmon resonance (SPR)-binding assays and in silico docking. Stat3‑binding assay indicated that EGCG significantly interrupted Stat3 peptide binding at micromolar concentrations, and the docking experiments indicated that EGCG had a strong interaction with Arg-609, one of the key residues in the STAT3 SH2 domain that contributes greatly to Stat3 and phosphorylated peptide binding. Following treatment of the hepatocellular carcinoma cell lines BEL-7402 and QGY-7703 with EGCG, in vitro, EGCG significantly suppressed cell proliferation as detected by MTT assay, induced apoptosis as detected by flow cytometry, dramatically lowered the expression levels of phosphorylated Stat3 proteins (p-Stat3) as determined by immunoblot detection, and inhibited the expression of multiple genes including Bcl-xL, c-Myc, VEGF and cyclin D1 as demonstrated by RT-PCR analysis. In conclusion, our research data indicate that the anticancer function of green tea results from the inhibition of the STAT3 signaling pathway by EGCG.

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