Dehydrocostus lactone as Cyclooxygenase-2 specific inhibitor

1010 Cyclooxygenase-2 (COX-2) gene encodes an inducible enzyme that converts arachidonic acid to prostaglandins and is up-regulated in colorectal neoplasms. Large scale of retrospective and prospective studies has showed that COX-2 inhibitors decrease colorectal cancer incidence and mortality. The aim of this study is to determine whether dehydrocostus lactone purified from plant can act as the selective inhibitor and their potential use as new anti-cancer drugs. Dehydrocostus lactone is a sesquiterpene compound isolated from Sassurea lappa Clarks, which has been widely used as a medicinal plant in China, Korea and India. Our research shows that dehydrocostus lactone can inhibit PGE2 synthesis by 42% in vitro, comparing with a 33% inhibition by Indomethacin, using PGE2 specific Competitive Enzyme Immunoassay. The inhibition is specific as the chemical does not inhibit cyclooxygenase-1. In vivo study indicates that dehydrocostus lactone suppresses the growth of colorecral cancer xenografts transplanted by colon cancer cell line colo205 in athymic mice. The inhibition effect was dose dependent, with 18% reduction in 5mg/kg/day group, and 46% reduction in 10mg/kg/day (p