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 Publisher Pubmed



Panji M¹ ; Behmard V² ; Zare Z³ ; Malekpour M⁴ ; Nejadbiglari H⁵ ; Yavari S⁶ ; Nayerpour Dizaj T⁷ ; Safaeian A⁸ ; Maleki N⁹ ; Abbasi M^{10, 11} ; Abazari O¹² ; Shabanzadeh M¹³ ; Khanicheragh P¹⁴
Source: Gene Published:2021

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. © 2021 Elsevier B.V.