title: Epicatechin-3-gallate reverses TGF-β1-induced epithelial-to-mesenchymal transition and inhibits cell invasion and protease activities in human lung cancer cells.
abstract: Epithelial-to-mesenchymal transition (EMT) and invasion potential have been considered as essential factors in cancer metastasis, which is the major cause of cancer death. EMT is a multi-step process that involves gain invasion, cytoskeleton change, cell adhesion, and proteolytic extracellular matrix degradation. Epicatechin-3-gallate (ECG), which is a natural polyphenolic component of green tea, elicits several antioxidant and anti-inflammatory effects. However, the effects of ECG on cancer invasion and EMT of human lung carcinoma remain unknown. We provided molecular evidence supporting the anti-metastatic effect of ECG. This compound suppressed the invasion (P < 0.001) of highly metastatic A549 cells by reducing the activities of matrix metalloproteinase-2 (P < 0.001) and urokinasetype plasminogen activator (P < 0.001). ECG also reversed the transforming growth factor (TGF)-β1-induced EMT and upregulated epithelial markers, such as E-cadherin. Conversely, ECG inhibited mesenchymal markers, such as fibronectin and p-FAK. The subcutaneous inoculation of this compound also inhibited the tumor growth of the A549 cells in vivo. Therefore, ECG may be used as an anti-cancer and anti-invasion agent for the adjuvant treatment and metastasis control of human lung cancer cells. ECG may also be administered as an effective chemopreventive agent against TGF-β1-induced EMT.
authors.affiliation: Department of Medicine Chest, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan.
authors.forename: Shu-Fang
authors.initials: SF
authors.lastname: Huang
authors.affiliation: Medical Education Center, Kaohsiung Armed Forces General Hospital, Kaohsiung City, Taiwan; Institute of Biochemistry, Microbiology and Immunology, Chung Shang Medical University, Taichung City, Taiwan.
authors.forename: Chi-Ting
authors.initials: CT
authors.lastname: Horng
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung Shang Medical University, Taichung City, Taiwan.
authors.forename: Yih-Shou
authors.initials: YS
authors.lastname: Hsieh
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung Shang Medical University, Taichung City, Taiwan.
authors.forename: Yi-Hsien
authors.initials: YH
authors.lastname: Hsieh
authors.affiliation: Institute and Department of Food Science, Central Taiwan University of Science and Technology, Taiwan.
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Chu
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung Shang Medical University, Taichung City, Taiwan; Clinical Laboratory, Chung Shan Medical University Hospital, No 110, Section 1, Jianguo N. Road, Taichung, Taiwan. Electronic address: peini@csmu.edu.tw.
authors.forename: Pei-Ni
authors.initials: PN
authors.lastname: Chen
mesh_terms: D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D051379:Mice; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D053773:Transforming Growth Factor beta1; D002392:Catechin; C062669:epicatechin gallate; D020778:Matrix Metalloproteinase 2
keywords: ECG; EMT; Lung cancer; Metastasis; Polyphenol