Mechanism of the inhibition of the STAT3 signaling pathway by EGCG.
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.
Huaihe Hospital, Henan University, Kaifeng 475000, P.R. China.
Yang
Y
Wang
Xuequn
X
Ren
Chaoyang
C
Deng
Lu
L
Yang
Erfu
E
Yan
Tao
T
Guo
Yanmin
Y
Li
Marvin Xuejun
MX
Xu
D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology; D062105:Molecular Docking Simulation; D010766:Phosphorylation / Q000187:drug effects; D011487:Protein Conformation; D050796:STAT3 Transcription Factor / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D020349:Surface Plasmon Resonance; D013662:Tea / Q000737:chemistry; D018909:src Homology Domains / Q000187:drug effects
D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate