Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2004-8-17
pubmed:abstractText
Aberrant arachidonic acid metabolism is involved in the inflammatory and carcinogenic processes. In this study, we investigated the effects of curcumin, a naturally occurring chemopreventive agent, and related beta-diketone derivatives on the release of arachidonic acid and its metabolites in the murine macrophage RAW264.7 cells and in HT-29 human colon cancer cells. We also examined their effects on the catalytic activities and protein levels of related enzymes: cytosolic phospholipase A(2) (cPLA(2)), cyclooxygenases (COX) as well as 5-lipoxygenase (5-LOX). At 10 micro M, dibenzoylmethane (DBM), trimethoxydibenzoylmethane (TDM), tetrahydrocurcumin (THC) and curcumin effectively inhibited the release of arachidonic acid and its metabolites in lipopolysaccharide (LPS)-stimulated RAW cells and A23187-stimulated HT-29 cells. Inhibition of phosphorylation of cPLA(2), the activation process of this enzyme, rather than direct inhibition of cPLA(2) activity appears to be involved in the effect of curcumin. All the curcuminoids (10 micro M) potently inhibited the formation of prostaglandin E(2) (PGE(2)) in LPS-stimulated RAW cells. Curcumin (20 micro M) significantly inhibited LPS-induced COX-2 expression; this effect, rather than the catalytic inhibition of COX, may contribute to the decreased PGE(2) formation. Without LPS-stimulation, however, curcumin increased the COX-2 level in the macrophage cells. Studies with isolated ovine COX-1 and COX-2 enzymes showed that the curcuminoids had significantly higher inhibitory effects on the peroxidase activity of COX-1 than that of COX-2. Curcumin and THC potently inhibited the activity of human recombinant 5-LOX, showing estimated IC(50) values of 0.7 and 3 micro M, respectively. The results suggest that curcumin affects arachidonic acid metabolism by blocking the phosphorylation of cPLA(2), decreasing the expression of COX-2 and inhibiting the catalytic activities of 5-LOX. These activities may contribute to the anti-inflammatory and anticarcinogenic actions of curcumin and its analogs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Arachidonate 5-Lipoxygenase, http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Benzoates, http://linkedlifedata.com/resource/pubmed/chemical/Chalcones, http://linkedlifedata.com/resource/pubmed/chemical/Curcumin, http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides, http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A, http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases, http://linkedlifedata.com/resource/pubmed/chemical/dibenzoylmethane
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1671-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15073046-Animals, pubmed-meshheading:15073046-Antineoplastic Agents, pubmed-meshheading:15073046-Arachidonate 5-Lipoxygenase, pubmed-meshheading:15073046-Arachidonic Acid, pubmed-meshheading:15073046-Benzoates, pubmed-meshheading:15073046-Cells, Cultured, pubmed-meshheading:15073046-Chalcones, pubmed-meshheading:15073046-Colonic Neoplasms, pubmed-meshheading:15073046-Curcumin, pubmed-meshheading:15073046-Cytosol, pubmed-meshheading:15073046-Dinoprostone, pubmed-meshheading:15073046-Enzyme Inhibitors, pubmed-meshheading:15073046-Humans, pubmed-meshheading:15073046-Lipopolysaccharides, pubmed-meshheading:15073046-Macrophages, pubmed-meshheading:15073046-Phospholipases A, pubmed-meshheading:15073046-Phosphorylation, pubmed-meshheading:15073046-Prostaglandin-Endoperoxide Synthases, pubmed-meshheading:15073046-Sheep
pubmed:year
2004
pubmed:articleTitle
Modulation of arachidonic acid metabolism by curcumin and related beta-diketone derivatives: effects on cytosolic phospholipase A(2), cyclooxygenases and 5-lipoxygenase.
pubmed:affiliation
Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
pubmed:publicationType
Journal Article, Comparative Study