title: Epigallocatechin-3-gallate inhibits nicotine-induced migration and invasion by the suppression of angiogenesis and epithelial-mesenchymal transition in non-small cell lung cancer cells.
abstract: Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea extract, has been found to have anticancer activities in various types of cancer. However, the underlying mechanisms are not completely clear. In the present study, the effects of EGCG on migration, invasion, angiogenesis and epithelial-mesenchymal transition (EMT) induced by nicotine in A549 non-small cell lung cancer (NSCLC) cells were investigated, and the underlying molecular mechanisms were preliminarily examined. The results showed that different concentrations of EGCG significantly inhibited nicotine-induced migration and invasion. Moreover, EGCG reversed the upregulation of HIF-1α, vascular endothelial growth factor (VEGF), COX-2, p-Akt, p-ERK and vimentin protein levels and the downregulation of p53 and β-catenin protein levels mediated by nicotine in A549 cells, but had no significant effect on their mRNA levels. Furthermore, EGCG markedly inhibited HIF-1α-dependent angiogenesis induced by nicotine in vitro and in vivo, and suppressed HIF-1α and VEGF protein expression induced by nicotine in A549 xenografts of nude mice. Taken together, the results indicated that EGCG inhibited nicotine-induced angiogenesis and EMT, leading to migration and invasion in A549 cells. The results of the present study suggested that EGCG can be developed into a potential agent for the prevention and treatment of smoking-associated NSCLC.
authors.affiliation: Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, Guangdong 524023, P.R. China.
authors.forename: Jingli
authors.initials: J
authors.lastname: Shi
authors.affiliation: Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, Guangdong 524023, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, Guangdong 524023, P.R. China.
authors.forename: Wenzhang
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, Guangdong 524023, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, Guangdong 524023, P.R. China.
authors.forename: Bihua
authors.initials: B
authors.lastname: Lin
authors.affiliation: Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, Guangdong 524023, P.R. China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Tang
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009538:Nicotine / Q000633:toxicity; D012907:Smoking / Q000009:adverse effects; D013662:Tea; D023041:Xenograft Model Antitumor Assays
chemical_list: D009363:Neoplasm Proteins; D013662:Tea; D009538:Nicotine; D002392:Catechin; C045651:epigallocatechin gallate