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Resveratrol inhibits TGF-β1-induced epithelial-to-mesenchymal transition and suppresses lung cancer invasion and metastasis.
Toxicology. 2013 Jan 07; 303:139-46.T

Abstract

Epithelial-to-mesenchymal transition (EMT) is a cellular process during which epithelial polarized cells become motile mesenchymal-appearing cells, which in turn promotes carcinoma invasion and metastasis. Resveratrol (trans-3,4',5-trihydroxystilbene) is a natural polyphenolic compound found in grapes, red wine and several other plants. Numerous reports in the literature indicate that resveratrol can suppress cancer invasion and metastasis. However, the underlying mechanisms of inhibiting metastasis by resveratrol are complex, not fully elucidated and the subject of intense scientific debate. Despite evidence indicating that EMT can be a target for resveratrol, little is known about the effect of resveratrol on lung cancer cells. Our previous studies demonstrated that TGF-β1 induces EMT to promote lung adenocarcinoma invasion and metastasis. To understand the repressive role of resveratrol in lung cancer invasion and metastasis, we sought to investigate the potential use of resveratrol as an inhibitor of TGF-β1-induced EMT development in A549 lung cancer cells in vitro. Here we show that when A549 cells are treated with TGF-β1 and resveratrol, the latter inhibits the initiation of TGF-β1-induced EMT. Our results show that 20 μM resveratrol increases expression of the epithelial phenotype marker E-cadherin and represses the expression of the mesenchymal phenotype markers, Fibronectin and Vimentin during the initiation of TGF-β1-induced EMT. Resveratrol also inhibits expression of EMT-inducing transcription factors Snail1 and Slug, although the expression of the Twist1 transcription factor remained unchanged. Resveratrol inhibits the TGF-β1-induced increase in cell adhesion, migration and invasion of A549 lung cancer cells. Taken together, our findings provide new evidence that resveratrol suppresses lung cancer invasion and metastasis in vitro through inhibiting TGF-β1-induced EMT.

Authors+Show Affiliations

Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai 200433, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23146760

Citation

Wang, Heyong, et al. "Resveratrol Inhibits TGF-β1-induced Epithelial-to-mesenchymal Transition and Suppresses Lung Cancer Invasion and Metastasis." Toxicology, vol. 303, 2013, pp. 139-46.
Wang H, Zhang H, Tang L, et al. Resveratrol inhibits TGF-β1-induced epithelial-to-mesenchymal transition and suppresses lung cancer invasion and metastasis. Toxicology. 2013;303:139-46.
Wang, H., Zhang, H., Tang, L., Chen, H., Wu, C., Zhao, M., Yang, Y., Chen, X., & Liu, G. (2013). Resveratrol inhibits TGF-β1-induced epithelial-to-mesenchymal transition and suppresses lung cancer invasion and metastasis. Toxicology, 303, 139-46. https://doi.org/10.1016/j.tox.2012.09.017
Wang H, et al. Resveratrol Inhibits TGF-β1-induced Epithelial-to-mesenchymal Transition and Suppresses Lung Cancer Invasion and Metastasis. Toxicology. 2013 Jan 7;303:139-46. PubMed PMID: 23146760.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Resveratrol inhibits TGF-β1-induced epithelial-to-mesenchymal transition and suppresses lung cancer invasion and metastasis. AU - Wang,Heyong, AU - Zhang,Huijun, AU - Tang,Liang, AU - Chen,Haixia, AU - Wu,Chunlian, AU - Zhao,Mingchuan, AU - Yang,Yaoqin, AU - Chen,Xiaofeng, AU - Liu,Gentao, Y1 - 2012/11/09/ PY - 2012/08/16/received PY - 2012/09/18/revised PY - 2012/09/24/accepted PY - 2012/11/14/entrez PY - 2012/11/14/pubmed PY - 2013/3/8/medline SP - 139 EP - 46 JF - Toxicology JO - Toxicology VL - 303 N2 - Epithelial-to-mesenchymal transition (EMT) is a cellular process during which epithelial polarized cells become motile mesenchymal-appearing cells, which in turn promotes carcinoma invasion and metastasis. Resveratrol (trans-3,4',5-trihydroxystilbene) is a natural polyphenolic compound found in grapes, red wine and several other plants. Numerous reports in the literature indicate that resveratrol can suppress cancer invasion and metastasis. However, the underlying mechanisms of inhibiting metastasis by resveratrol are complex, not fully elucidated and the subject of intense scientific debate. Despite evidence indicating that EMT can be a target for resveratrol, little is known about the effect of resveratrol on lung cancer cells. Our previous studies demonstrated that TGF-β1 induces EMT to promote lung adenocarcinoma invasion and metastasis. To understand the repressive role of resveratrol in lung cancer invasion and metastasis, we sought to investigate the potential use of resveratrol as an inhibitor of TGF-β1-induced EMT development in A549 lung cancer cells in vitro. Here we show that when A549 cells are treated with TGF-β1 and resveratrol, the latter inhibits the initiation of TGF-β1-induced EMT. Our results show that 20 μM resveratrol increases expression of the epithelial phenotype marker E-cadherin and represses the expression of the mesenchymal phenotype markers, Fibronectin and Vimentin during the initiation of TGF-β1-induced EMT. Resveratrol also inhibits expression of EMT-inducing transcription factors Snail1 and Slug, although the expression of the Twist1 transcription factor remained unchanged. Resveratrol inhibits the TGF-β1-induced increase in cell adhesion, migration and invasion of A549 lung cancer cells. Taken together, our findings provide new evidence that resveratrol suppresses lung cancer invasion and metastasis in vitro through inhibiting TGF-β1-induced EMT. SN - 1879-3185 UR - https://www.unboundmedicine.com/medline/citation/23146760/Resveratrol_inhibits_TGF_β1_induced_epithelial_to_mesenchymal_transition_and_suppresses_lung_cancer_invasion_and_metastasis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300-483X(12)00373-3 DB - PRIME DP - Unbound Medicine ER -