Inhibition of cytokine-induced prostanoid biogenesis by phytochemicals in human colonic fibroblasts.
Many of the inflammatory pathways regulating the production of prostanoids are implicated in the development of colon cancer. Diets rich in fruits and vegetables are associated with decreased rates of colon cancer and this may reflect anti-inflammatory properties of some phytochemicals in plant-based foods. In order to ascertain which of the many dietary compounds may be protective, a cell-based screening method was established to determine their effects on the production of prostanoids. By up-regulating prostaglandin H synthase-2 in human colonic fibroblast cells with cytokines, we have investigated the potential protective effect of a structurally related group of phytochemicals on prostanoid biogenesis. Several of the compounds significantly inhibited prostanoid biogenesis, by up to 81% and others enhanced prostanoid production. All of the compounds that enhanced prostanoid production belonged to the hydroxylated benzoic acid family and good correlation was observed with their redox activity and the ability to enhance prostanoid production. Common structural features of the inhibitors were the presence of 4-hydroxyl and 3-methoxyl substituents on the aromatic ring and/or the presence of a three-carbon side-chain on C1.
Russell
Wendy R
WR
Gut Health Division, Molecular Nutrition Group, Rowett Research Institute, Bucksburn, Aberdeen AB21 9SB, Scotland, UK. W.Russell@rowett.ac.uk
Drew
Janice E
JE
Scobbie
Lorraine
L
Duthie
Garry G
GG
D002478:Cells, Cultured; D003106:Colon / Q000166:cytology* / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D018514:Plant Structures / Q000737:chemistry / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D015854:Up-Regulation / Q000235:genetics
D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D011453:Prostaglandins; D051546:Cyclooxygenase 2