Indomethacin antagonizes EP₂ prostanoid receptor activation in LS174T human colon cancer cells

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• 作者：Yuta Ikawa ; Hiromichi Fujino ; ^{fujino@p.chiba-u.ac.jp} ; Sho Otake ; Toshihiko Murayama
• 关键词：Indomethacin ; EP2 prostanoid receptor ; Colon cancer ; COX-inhibition-independent effect ; NSAID ; G protein-coupled receptor
• 刊名：European Journal of Pharmacology
• 出版年：2012
• 期刊代码：24_00142999
• 类别：neu
• 出版时间：5 April, 2012
• 卷：680
• 期：1-3
• 页码：16-21
• 文件大小：684 K

摘要

Increases in the level of cyclooxygenase (COX)-2 and prostanoids such as prostaglandin E₂ (PGE₂) are considered biomarkers of colorectal cancer. Therefore, non-steroidal anti-inflammatory drugs (NSAID) have been used to reduce the risk of cancer development by reducing prostanoid biosynthesis as COX inhibitors. Along with their activity as COX inhibitors, NSAID have been reported to have other effects. One major NSAID, indomethacin, has been shown to have several effects independent of COX inhibition. To further examine the COX-inhibition-independent effects of indomethacin on colorectal cancer, we used human colon cancer LS174T cells, known to have express little COX-2 and have no detectable PGE₂ production. Here we show that indomethacin has a potential antagonizing effect on human EP₂ receptors. We believe this study raises the reasons to use indomethacin as a lead-compound for setting up another EP₂ receptor-specific antagonist as a relatively cost-efficient strategy for anti-cancer medication in the future.