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  • Title: Suppressing effects of green tea extract and Epigallocatechin-3-gallate (EGCG) on TGF-β- induced Epithelial-to-mesenchymal transition via ROS/Smad signaling in human cervical cancer cells.
    Author: Panji M, Behmard V, Zare Z, Malekpour M, Nejadbiglari H, Yavari S, Nayerpour Dizaj T, Safaeian A, Maleki N, Abbasi M, Abazari O, Shabanzadeh M, Khanicheragh P.
    Journal: Gene; 2021 Aug 20; 794():145774. PubMed ID: 34126197.
    Abstract:
    BACKGROUND: Transforming growth factor-β (TGF-β)-induced Epithelial-to-mesenchymal transition (EMT) process is a fundamental target for preventing cervical cancer cells' progression and invasion. Green tea and its principal active substance, Epigallocatechin-3-gallate (EGCG), demonstrate anti-tumor activities in various tumor cells. METHODS: The cell viability of two cervical cancer cell lines, Hela and SiHa, in the experimental groups was examined employing the MTT method, and ROS generation was probed applying 2',7'-dichlorofluorescein diacetate-based assay. The Smad signaling and EMT process was evaluated utilizing western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR). Chromatin immunoprecipitation (ChIP) and Smad binding element (SBE)-luciferase assays were employed to measure Smad-DNA interaction and Smad transcriptional activity, respectively. RESULTS: EGCG (0-100 μmol/L) and green tea extract (0-250 μg/ml) suppressed the viability of cancer cells in a dose-dependent manner (p < 0.01). Our conclusions affirmed that pre-incubation with green tea extract (80 μg/ml) and EGCG (60 μmol/L) significantly reversed the impacts of TGF-β in Hela and SiHa cells by decreasing Vimentin, ZEB, Slug, Snail, and Twist and increasing E-cadherin expression. The molecular mechanism of green tea extract and EGCG for TGF-β-induced EMT inhibition interfered with ROS generation and Smad signaling. Green tea extract and EGCG could significantly decrease ROS levels, the phosphorylation of Smad2/3, the translocation, DNA binding, and activity of Smads in cervical cancer cell lines treated with TGF-β1 (p < 0.01). CONCLUSION: EGCG and green tea extract suppressed TGF-β-induced EMT in Hela and SiHa cells, and the underlying molecular mechanism may be related to the ROS generation and Smad signaling pathway.
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