Inhibition of cytokine-induced prostanoid biogenesis by phytochemicals in human colonic fibroblasts

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Abstract

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. (c) 2005 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)124-130
Number of pages7
JournalBiochimica et Biophysica Acta. Molecular Basis of Disease : BBA
Volume1762
Issue number1
Early online date2 Sep 2005
DOIs
Publication statusPublished - Jan 2006

Keywords

  • colon cancer
  • prostaglandin H synthase
  • cyclooxygenase
  • inflamation
  • IL-1 beta
  • phenylpropanoid
  • COX-2 inhibitors
  • cyclooxygenase-2 expression
  • colorectal adenomas
  • cancer
  • risk
  • chemoprevention
  • events

Cite this

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title = "Inhibition of cytokine-induced prostanoid biogenesis by phytochemicals in human colonic fibroblasts",
abstract = "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. (c) 2005 Elsevier B.V. All rights reserved.",
keywords = "colon cancer, prostaglandin H synthase, cyclooxygenase, inflamation, IL-1 beta, phenylpropanoid, COX-2 inhibitors, cyclooxygenase-2 expression, colorectal adenomas, cancer, risk, chemoprevention, events",
author = "Russell, {Wendy R.} and Janice Drew and Lorraine Scobbie and Duthie, {Garry G.}",
year = "2006",
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T1 - Inhibition of cytokine-induced prostanoid biogenesis by phytochemicals in human colonic fibroblasts

AU - Russell, Wendy R.

AU - Drew, Janice

AU - Scobbie, Lorraine

AU - Duthie, Garry G.

PY - 2006/1

Y1 - 2006/1

N2 - 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. (c) 2005 Elsevier B.V. All rights reserved.

AB - 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. (c) 2005 Elsevier B.V. All rights reserved.

KW - colon cancer

KW - prostaglandin H synthase

KW - cyclooxygenase

KW - inflamation

KW - IL-1 beta

KW - phenylpropanoid

KW - COX-2 inhibitors

KW - cyclooxygenase-2 expression

KW - colorectal adenomas

KW - cancer

KW - risk

KW - chemoprevention

KW - events

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M3 - Article

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SP - 124

EP - 130

JO - Biochimica et Biophysica Acta. Molecular Basis of Disease : BBA

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