Suppression of cyclooxygenase-2 gene transcription by humulon of beer hop extract studied with reference to glucocorticoid.
In murine osteoblastic MC3T3-E1 cells which produced prostaglandin E2 as a bone resorption factor, the cyclooxygenase-2 induction by tumor necrosis factor alpha (TNFalpha) was suppressed by dexamethasone with an IC(50) of 1 nM. Humulon isolated from hop extract for beer brewing was reported previously as an inhibitor of bone resorption [Tobe, H. et al. (1997) Biosci. Biotech. Biochem. 61, 158-159]. We showed that the compound suppressed the TNFalpha-dependent cyclooxygenase-2 induction with an IC(50) of as low as about 30 nM as demonstrated experimentally by catalytic activity assay, Northern blot analysis and promoter analysis. Reporter gene experiments suggested that humulon blocked the cyclooxygenase-2 expression mediated by NFkappaB and NF-IL6, but the intracellular glucocorticoid receptor was not involved. The catalytic activity of cyclooxygenase-2 was inhibited by humulon with an IC(50) of as high as 1.6 microM. These results showed that humulon suppressed cyclooxygenase-2 induction at the step of transcription.
Yamamoto
K
K
Department of Biochemistry, The University of Tokushima, School of Medicine, Tokushima, Japan. kei@basic.med.tokushima-u.ac.jp
Wang
J
J
Yamamoto
S
S
Tobe
H
H
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001515:Beer / Q000032:analysis*; D001862:Bone Resorption; D022762:CCAAT-Enhancer-Binding Proteins; D002384:Catalysis; D053138:Cyclohexenes; D051546:Cyclooxygenase 2; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013729:Terpenes / Q000302:isolation & purification / Q000494:pharmacology*; D013937:Thymidine Kinase / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*
D022762:CCAAT-Enhancer-Binding Proteins; D053138:Cyclohexenes; D017931:DNA Primers; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D016328:NF-kappa B; D009687:Nuclear Proteins; D012333:RNA, Messenger; D013729:Terpenes; D003907:Dexamethasone; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D013937:Thymidine Kinase; D015232:Dinoprostone; C007966:humulon