Joonwoo Park1, Myeong Kuk Shim1, Mirim Jin2, Mee-Ra Rhyu3, YoungJoo Lee4. 1. Department of Bioscience and Biotechnology, College of Life Science, Sejong University, Kwangjingu, Kunjadong, Seoul 143-747, Republic of Korea. 2. Laboratory of Pharmacology, College of Korean Medicine, Daejeon University, Daejeon 301-724, Republic of Korea. 3. Division of Metabolism and Functionality Research, Korea Food Research Institute, Sungnam 463-746, Republic of Korea. Electronic address: mrrhyu@kfri.re.kr. 4. 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.
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. PURPOSE: This study examined the effects of methyl syringate on hypoxia-induced COX-2 in human distal lung epithelial A549 cells. STUDY DESIGN: 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. CONCLUSION: 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.
BACKGROUND: We have previously found that methyl syringate is a specific and selective agonist of the humantransient 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. PURPOSE: This study examined the effects of methyl syringate on hypoxia-induced COX-2 in human distal lung epithelial A549 cells. STUDY DESIGN: 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. CONCLUSION: 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.