Intervention of a Communication Between PI3K/Akt and β-Catenin by (-)-Epigallocatechin-3-Gallate Suppresses TGF-β1-Promoted Epithelial-Mesenchymal Transition and Invasive Phenotype of NSCLC Cells.

IF 4.4 3区 医学 Q2 ENVIRONMENTAL SCIENCES
Li-Sung Hsu, Chih-Li Lin, Min-Hsiung Pan, Wei-Jen Chen
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引用次数: 0

Abstract

The epithelial-mesenchymal transition (EMT) assists in the acquisition of invasiveness, relapse, and resistance in non-small cell lung cancer (NSCLC) and can be caused by the signaling of transforming growth factor-β1 (TGF-β1) through Smad-mediated or Smad-independent pathways. (-)-Epigallocatechin-3-gallate (EGCG), a multifunctional cancer-preventing bioconstituent found in tea polyphenols, has been shown to repress TGF-β1-triggered EMT in the human NSCLC A549 cell line by inhibiting the activation of Smad2 and Erk1/2 or reducing the acetylation of Smad2 and Smad3. However, its impact on the Smad-independent pathway remains unclear. Here, we found that EGCG, similar to LY294002 (a specific inhibitor of phosphatidylinositol 3-kinase [PI3K]), downregulated Akt activation and restored the action of glycogen synthase kinase-3β (GSK-3β), accompanied by TGF-β1-caused changes in hallmarks of EMT such as N-cadherin, E-cadherin, vimentin, and Snail in A549 cells. EGCG inhibited β-catenin expression and its nuclear localization caused by TGF-β1, suggesting that EGCG blocks the crosstalk between the PI3K/Akt/GSK-3β route and β-catenin. Furthermore, it was shown that EGCG suppressed TGF-β1-elicited invasive phenotypes of A549 cells, including invading and migrating activities, matrix metalloproteinase-2 (MMP-2) secretion, cell adhesion, and wound healing. In summary, we suggest that EGCG inhibits the induction of EMT by TGF-β1 in NSCLC not only through a Smad-dependent pathway, but also through the regulation of the PI3K/Akt/β-catenin signaling axis.

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来源期刊
Environmental Toxicology
Environmental Toxicology 环境科学-毒理学
CiteScore
7.10
自引率
8.90%
发文量
261
审稿时长
4.5 months
期刊介绍: The journal publishes in the areas of toxicity and toxicology of environmental pollutants in air, dust, sediment, soil and water, and natural toxins in the environment.Of particular interest are: Toxic or biologically disruptive impacts of anthropogenic chemicals such as pharmaceuticals, industrial organics, agricultural chemicals, and by-products such as chlorinated compounds from water disinfection and waste incineration; Natural toxins and their impacts; Biotransformation and metabolism of toxigenic compounds, food chains for toxin accumulation or biodegradation; Assays of toxicity, endocrine disruption, mutagenicity, carcinogenicity, ecosystem impact and health hazard; Environmental and public health risk assessment, environmental guidelines, environmental policy for toxicants.
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