Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2019913 | Prostaglandins & Other Lipid Mediators | 2009 | 6 Pages |
Abstract
Accumulating evidence suggests that cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) may play an important role in colon carcinogenesis. Thus, blockage of this pathway may be a suitable strategy for colon cancer chemoprevention. Recent clinical studies suggest that COX-2 inhibitors cause adverse cardiovascular effects due to prostacyclin (PGI2) inhibition. To test our hypothesis that inhibition of PGE2 signaling through E-prostanoid (EP) receptors may offer a safer cardiovascular profile than COX-2 inhibition, we analyzed expression of 6-keto PGF1α, a hydrated form of PGI2 and PGI2 synthase, which was stimulated with cytokines in human umbilical vein endothelial cells (HUVECs) treated with the EP1 receptor antagonist ONO-8711 or the COX-2 inhibitor celecoxib. ONO-8711 did not inhibit both 6-keto PGF1α production and PGIS expression, whereas celecoxib did in HUVECs. ONO-8711 also inhibited cytokine-induced tissue factor expression in HUVECs. These results suggest that ONO-8711 may be a safer chemopreventive agent with respect to cardiovascular events.
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Authors
Tatsuya Kaneshiro, Masae Okumura, Samer Maalouf, Andre Uflacker, Takayuki Maruyama, Toshihiko Kawamori,