title: Rubus idaeus L. reverses epithelial-to-mesenchymal transition and suppresses cell invasion and protease activities by targeting ERK1/2 and FAK pathways in human lung cancer cells.
abstract: Epithelial to mesenchymal transition (EMT) has been considered essential for cancer metastasis, a multistep complicated process including local invasion, intravasation, extravasation, and proliferation at distant sites. Herein we provided molecular evidence associated with the antimetastatic effect of Rubus idaeus L. extracts (RIE) by showing a nearly complete inhibition on the invasion (p<0.001) of highly metastatic A549 cells via reduced activities of matrix metalloproteinase-2 (MMP-2) and urokinasetype plasminogen activator (u-PA). We performed Western blot to find that RIE could induce up-regulation of epithelial marker such as E-cadherin and α-catenin and inhibit the mesenchymal markers such as N-cadherin, fibronectin, snail-1, and vimentin. Selective snail-1 inhibition by snail-1-specific-siRNA also showed increased E-cadherin expression in A549 cells suggesting a possible involvement of snail-1 inhibition in RIE-caused increase in E-cadherin level. RIE also inhibited p-FAK, p-paxillin and AP-1 by Western blot analysis, indicating the anti-EMT effect of RIE in human lung carcinoma. Importantly, an in vivo BALB/c nude mice xenograft model showed that RIE treatment reduced tumor growth by oral gavage, and RIE represent promising candidates for future phytochemical-based mechanistic pathway-targeted cancer prevention strategies.
authors.affiliation: Clinical Laboratory, Chung Shan Medical University Hospital, No. 110, Section 1, Jianguo N. Road, Taichung, Taiwan; Institute of Biochemistry and Biotechnology, Chung Shan Medical University, No. 110, Section 1, Jianguo N. Road, Taichung, Taiwan.
authors.forename: Yih-Shou
authors.initials: YS
authors.lastname: Hsieh
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Chu
authors.forename: Li-Sung
authors.initials: LS
authors.lastname: Hsu
authors.forename: Kuo-Shuen
authors.initials: KS
authors.lastname: Chen
authors.forename: Ming-Tsung
authors.initials: MT
authors.lastname: Lai
authors.forename: Chia-Heng
authors.initials: CH
authors.lastname: Yeh
authors.forename: Pei-Ni
authors.initials: PN
authors.lastname: Chen
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D010936:Plant Extracts / Q000494:pharmacology; D065856:Rubus / Q000737:chemistry*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D015820:Cadherins; D010936:Plant Extracts; C000604407:SNAI1 protein, human; C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2
keywords: EMT; FAK; Invasion; MMP; MMP-2; RIE; Rubus idaeus; Rubus idaeus L. extracts; epithelial–mesenchymal transition; focal adhesion kinase; matrix metalloproteinase; u-PA; urokinasetype plasminogen activator