title: Geraniin inhibits TGF-β1-induced epithelial-mesenchymal transition and suppresses A549 lung cancer migration, invasion and anoikis resistance.
abstract: The epithelial-mesenchymal transition (EMT) is an important cellular process during which epithelial polarized cells become motile mesenchymal-appeared cells, which, in turn, induces the metastatic of cancer. Geraniin is a polyphenolic component isolated from Phyllanthus amarus, which exhibits a wide range of pharmacological and physiological activities, such as antitumor, anti-hyperglycemic, anti-hypertensive, antimicrobial, and antiviral activities. However, the possible role of geraniin in the EMT is unclear. We investigated the effect of geraniin on the EMT. Transforming growth factor-beta 1 (TGF-β1) induces the EMT to promote lung adenocarcinoma migration, invasion, and anoikis resistance. To understand the suppressive role of geraniin in lung cancer migration, invasion, and anoikis resistance, we investigated the use of geraniin as inhibitors of TGF-β1-induced EMT in A549 lung cancer cells in vitro. Here, we show that geraniin remarkably increased expression of the epithelial marker E-cadherin and repressed Snail upregulation and expression of the mesenchymal marker N-cadherin and vimentin during the TGF-β1-induced EMT. Geraniin also inhibited the TGF-β1-induced increase in cell migration, invasion, and anoikis resistance of A549 lung cancer cells. Additionally, geraniin markedly inhibited TGF-β1-regulated activation of Smad2. Taken together, our findings provide new evidence that geraniin suppresses lung cancer migration, invasion, and anoikis resistance in vitro by inhibiting the TGF-β1-induced EMT.
authors.affiliation: Laboratory of Molecular Oncology, Cheil General Hospital & Women's Healthcare Center, Dankook University College of Medicine, Seoul, South Korea. Electronic address: drug9054@naver.com.
authors.forename: Hyeonseok
authors.initials: H
authors.lastname: Ko
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D023102:Anoikis / Q000187:drug effects*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000473:pathology; D029803:Phyllanthus / Q000737:chemistry; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005960:Glucosides; D047348:Hydrolyzable Tannins; D053773:Transforming Growth Factor beta1; C024603:Geraniin
keywords: Anoikis resistance; Epithelial–mesenchymal transition (EMT); Geraniin; Invasion; Lung cancer; Migration; Transforming growth factor-beta 1 (TGF-β1)