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Wang Y.,Henan University | Ren X.,Henan University | Deng C.,Shanghai McAry Biomedical Technology Co. | Yang L.,Shanghai McAry Biomedical Technology Co. | And 4 more authors.
Oncology Reports | Year: 2013

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. Source

Xu M.X.,Zhengzhou University | Zhao L.,Shanghai McAry Biomedical Technology Co. | Deng C.,Shanghai McAry Biomedical Technology Co. | Yang L.U.,Shanghai McAry Biomedical Technology Co. | And 5 more authors.
International Journal of Oncology | Year: 2013

Curcumin from the rhizome of Curcuma longa (zingiberaceae) has been reported to be a chemopreventive agent that affects cell proliferation by arresting the cell cycle in G2 and modulating the wnt signaling pathway. We found that curcumin inhibits proliferation and induces apoptosis of human hepatocellular carcinoma (HCC) cells in a concentration-dependent manner. We identified that curcumin interrupts wnt signaling by decreasing β-catenin activity, which in turn suppresses the expression of β-catenin target genes (c-myc, VEGF and cyclin D1). Our results from molecular simulation of curcumin binding to Dvl2 protein and from binding free energy calculations suggest that curcumin may prevent axin recruitment to cellular membrane in order to maintain the functional β-catenin destruction complex in normal cells. This results in β-catenin being unable to accumulate in the nucleus, depriving the protein of its ability to bind with lymphoid enhancer factor/T cell-specific transcription factor (Lef/Tcf) and repressing its activation of target gene transcription. This may be one mechanism through which curcumin inhibits proliferation and induces apoptosis of HCC cells. Source

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