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

Increases in the level of cyclooxygenase (COX)-2 and prostanoids such as prostaglandin E-2 (PGE(2)) 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 PGE(2) 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. (C) 2012 Elsevier B. V. All rights reserved.