Suppression of cyclooxygenase-2 gene transcription by humulon.

Abstract

Cyclooxygenase is the key enzyme in the biosynthetic pathway of prostaglandins (PGs) and thromboxane from arachidonic acid. There are two isozymes of cyclooxygenase; constitutive cyclooxygenase-1 and inducible cyclooxygenase-2.1’2MC3T3-E1 cell cloned from newborn mouse calvaria is an osteogenic cell line which differentiates into an osteoblast.3’4Our extensive studies demonstrated the production of PGE2as a major arachidonate metabolite in this cell linesand the induction of cyclooxygenase by various bioregulators including tumor necrosis factor a (TNFa).5-9Later the induced enzyme in MC3T3-E1 cells was identified as cyclooxygenase-2.8-10Previously humulon ((R)-3,5,6-trihydroxy-4,6-bis(3-methyl-2-butenyl)-2-(3-methyl-1oxobutyl)-2,4-cyclohexadien-1-one) (Fig. IA) isolated from hop (Humulus lupulus L.) extract was found as an inhibitor of bone resorption with an IC50of 5.9 nM.“ We noted this activity of humulon, and were interested in a possible inhibitory or suppressive effect of humulon on cyclooxygenase-2 leading to a decreased production of PGE2which is well known as a bone resorption factor.12