title: Molecular mechanism depressing PMA-induced invasive behaviors in human lung adenocarcinoma cells by cis- and trans-cinnamic acid.
abstract: Dietary polyphenols have been reported as an effective phytochemical for health protection and cinnamic acid (CA) is one of the polyphenols that has been demonstrated having chemopreventive potential. It was known that the early and distal metastasis might lead to the high mortality of patients with lung adenocarcinoma. We previously compared and verified the inhibitory effect of cis-CA and trans-CA on phorbol-12-myristate-13-acetate (PMA)-induced invasion of human lung adenocarcinoma A549 cells. The aim of this study was to explore the underlying molecular mechanism. By gelatin zymography and semi-quantitative RT-PCR, the activities and mRNA of MMP-9/MMP-2 exerted a significantly (p<.05) dose-dependent reduction by treating with cis-CA and trans-CA. Western blots further showed that the cis-CA- and trans-CA-inhibited MMPs might partly through modulating TIMP-1 and the PAI-2-regulated uPA activity. In molecular level, the AP-1 and NF-κB as well as the downstream of the MAPK pathway might be involved in cis-CA- and trans-CA-inhibited MMPs expression. This study disclosed the molecular mechanism underlying the anti-invasive activity of cis-CA and trans-CA and concluded the cis- and trans-form of CA should be a safe and potential agent to prevent lung tumor cells from metastasizing.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo North Rd., Taichung 40256, Taiwan; Tainan Hospital, Department of Health, Executive Yuan, No. 125, Zhongshan Rd., Tainan City 70043, Taiwan; Hualien Hospital, Department of Health, Executive Yuan, No. 600, Chungjen Rd., Hualien City, Hualien County 97061, Taiwan.
authors.forename: Chiung-Man
authors.initials: CM
authors.lastname: Tsai
authors.affiliation: Department of Health and Nutrition, ChiaNai University of Pharmacy and Science, No. 60, Sec. 1, Erh-jen Rd., Jen-te District, Tainan City 71710, Taiwan.
authors.forename: Fang-Ming
authors.initials: FM
authors.lastname: Sun
authors.affiliation: Graduate Institute of Applied Living Science, Tainan University of Technology, No. 529 Zhongzheng Rd., Yongkang District, Tainan City 71002, Taiwan.
authors.forename: Yen-Ling
authors.initials: YL
authors.lastname: Chen
authors.affiliation: School of Nutrition, Chung Shan Medical University and Department of Nutrition, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo North Rd., Taichung 40201, Taiwan.
authors.forename: Chin-Lin
authors.initials: CL
authors.lastname: Hsu
authors.affiliation: Department of Food Science and Biotechnology, National Chung Hsing University, No. 250 Kuokuang Rd., Taichung 40227, Taiwan. Electronic address: gcyen@nchu.edu.tw.
authors.forename: Gow-Chin
authors.initials: GC
authors.lastname: Yen
authors.affiliation: Graduate Institute of Applied Living Science, Tainan University of Technology, No. 529 Zhongzheng Rd., Yongkang District, Tainan City 71002, Taiwan. Electronic address: t10044@mail.tut.edu.tw.
authors.forename: Chia-Jui
authors.initials: CJ
authors.lastname: Weng
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D016588:Anticarcinogenic Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000633:toxicity; D045744:Cell Line, Tumor; D002934:Cinnamates / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009994:Osmolar Concentration; D013237:Stereoisomerism; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000633:toxicity; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D000972:Antineoplastic Agents, Phytogenic; D002273:Carcinogens; D002934:Cinnamates; D009363:Neoplasm Proteins; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C029010:cinnamic acid; C016658:phorbolol myristate acetate; D014568:Urokinase-Type Plasminogen Activator; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate