title: Methyl syringate, a TRPA1 agonist represses hypoxia-induced cyclooxygenase-2 in lung cancer cells.
abstract: BACKGROUND
  We have previously found that methyl syringate is a specific and selective agonist of the human transient receptor potential channel ankyrin 1 (TRPA1) and suppresses food intake and gastric emptying in imprinting control region mice. Because TRPA1 has been implicated in inflammatory responses, and inflammation and tumorigenesis are stimulated by the cyclooxygenase-2 (COX-2)/prostaglandin E2 pathway in hypoxic cancer cells.
  
  
  OBJECTIVE
  This study examined the effects of methyl syringate on hypoxia-induced COX-2 in human distal lung epithelial A549 cells.
  
  
  METHODS
  The effect of the methyl syringate on suppression of hypoxia-induced COX-2 in A549 cells were determined by Western blot and/or quantitative real-time polymerase chain reaction. The anti-invasive effect of methyl syringate was evaluated on A549 cells using matrigel invasion assay.
  
  
  RESULTS
  Methyl syringate suppressed hypoxia-induced COX-2 protein and mRNA expression and promoter activity and reduced hypoxia-induced cell migration and invasion and secretion of vascular endothelial growth factor. These effects were antagonized by a TRPA1 antagonist, implying their mediation by the TRPA1 pathway.
  
  
  CONCLUSIONS
  Together, these results indicate that methyl syringate inhibits the hypoxic induction of COX-2 expression and cell invasion through TRPA1 activation. These findings suggest that methyl syringate could be effective to suppress hypoxia-induced inflammation and indicate an additional functional effect of methyl syringate.
authors.affiliation: Department of Bioscience and Biotechnology, College of Life Science, Sejong University, Kwangjingu, Kunjadong, Seoul 143-747, Republic of Korea.
authors.forename: Joonwoo
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Bioscience and Biotechnology, College of Life Science, Sejong University, Kwangjingu, Kunjadong, Seoul 143-747, Republic of Korea.
authors.forename: Myeong Kuk
authors.initials: MK
authors.lastname: Shim
authors.affiliation: Laboratory of Pharmacology, College of Korean Medicine, Daejeon University, Daejeon 301-724, Republic of Korea.
authors.forename: Mirim
authors.initials: M
authors.lastname: Jin
authors.affiliation: Division of Metabolism and Functionality Research, Korea Food Research Institute, Sungnam 463-746, Republic of Korea. Electronic address: mrrhyu@kfri.re.kr.
authors.forename: Mee-Ra
authors.initials: MR
authors.lastname: Rhyu
authors.affiliation: Department of Bioscience and Biotechnology, College of Life Science, Sejong University, Kwangjingu, Kunjadong, Seoul 143-747, Republic of Korea. Electronic address: yjlee@sejong.ac.kr.
authors.forename: YoungJoo
authors.initials: Y
authors.lastname: Lee
mesh_terms: D015220:Calcium Channels; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002465:Cell Movement; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000819:agonists*; D011401:Promoter Regions, Genetic; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000819:agonists*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C506133:methyl syringate; D005707:Gallic Acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: Cyclooxygenase-2; Hypoxia; Methyl syringate; Sirtuin1; TRPA1