Methyl syringate, a TRPA1 agonist represses hypoxia-induced cyclooxygenase-2 in lung cancer cells

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• 作者：Joonwoo Park^a ; ¹ ; Myeong Kuk Shim^a ; ¹ ; Mirim Jin^b ; Mee-Ra Rhyu^c ; ^{mrrhyu@kfri.re.kr" class="auth_mail" title="E-mail the corresponding author} ; YoungJoo Lee^a ; ^{yjlee@sejong.ac.kr" class="auth_mail" title="E-mail the corresponding author} ; ^{yjlee8565@gmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Hypoxia ; Methyl syringate ; Sirtuin1 ; Cyclooxygenase-2 ; TRPA1
• 刊名：Phytomedicine
• 出版年：2016
• 出版时间：15 March 2016
• 年：2016
• 卷：23
• 期：3
• 页码：324-329
• 全文大小：1692 K

文摘

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.