Modulation of arachidonic acid metabolism by curcumin and related β-diketone derivatives

Effects on cytosolic phospholipase A2, cyclooxygenases and 5-lipoxygenase

Jungil Hong, Mousumi Bose, Jihyeung Ju, Jae Ha Ryu, Xiaoxin Chen, Shengmin Sang, Mao Jung Lee, Chung S. Yang

Research output: Contribution to journalArticleResearchpeer-review

306 Citations (Scopus)

Abstract

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 β-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 A2 (cPLA2), cyclooxygenases (COX) as well as 5-lipoxygenase (5-LOX). At 10 μM, 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 cPLA2, the activation process of this enzyme, rather than direct inhibition of cPLA2 activity appears to be involved in the effect of curcumin. All the curcuminoids (10 μM) potently inhibited the formation of prostaglandin E2 (PGE2) in LPS-stimulated RAW cells. Curcumin (20 μM) significantly inhibited LPS-induced COX-2 expression; this effect, rather than the catalytic inhibition of COX, may contribute to the decreased PGE2 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 IC50 values of 0.7 and 3 μM, respectively. The results suggest that curcumin affects arachidonic acid metabolism by blocking the phosphorylation of cPLA2, decreasing the expression of COX-2 and inhibiting the catalytic activities of 5-LOX. These activities may contribute to the antiinflammatory and anticarcinogenic actions of curcumin and its analogs.

Original languageEnglish
Pages (from-to)1671-1679
Number of pages9
JournalCarcinogenesis
Volume25
Issue number9
DOIs
StatePublished - 1 Sep 2004

Fingerprint

Cytosolic Phospholipases A2
Arachidonate 5-Lipoxygenase
Curcumin
Prostaglandin-Endoperoxide Synthases
Arachidonic Acid
Cyclooxygenase 2
Lipopolysaccharides
HT29 Cells
Cyclooxygenase 1
Dinoprostone
Macrophages
Phosphorylation
Enzyme Activation
Calcimycin
Enzymes
Human Activities
Colonic Neoplasms
Peroxidase
Inhibitory Concentration 50
Sheep

Cite this

Hong, Jungil ; Bose, Mousumi ; Ju, Jihyeung ; Ryu, Jae Ha ; Chen, Xiaoxin ; Sang, Shengmin ; Lee, Mao Jung ; Yang, Chung S. / Modulation of arachidonic acid metabolism by curcumin and related β-diketone derivatives : Effects on cytosolic phospholipase A2, cyclooxygenases and 5-lipoxygenase. In: Carcinogenesis. 2004 ; Vol. 25, No. 9. pp. 1671-1679.
@article{d84a0af8ab43440d98604d7effc60930,
title = "Modulation of arachidonic acid metabolism by curcumin and related β-diketone derivatives: Effects on cytosolic phospholipase A2, cyclooxygenases and 5-lipoxygenase",
abstract = "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 β-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 A2 (cPLA2), cyclooxygenases (COX) as well as 5-lipoxygenase (5-LOX). At 10 μM, 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 cPLA2, the activation process of this enzyme, rather than direct inhibition of cPLA2 activity appears to be involved in the effect of curcumin. All the curcuminoids (10 μM) potently inhibited the formation of prostaglandin E2 (PGE2) in LPS-stimulated RAW cells. Curcumin (20 μM) significantly inhibited LPS-induced COX-2 expression; this effect, rather than the catalytic inhibition of COX, may contribute to the decreased PGE2 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 IC50 values of 0.7 and 3 μM, respectively. The results suggest that curcumin affects arachidonic acid metabolism by blocking the phosphorylation of cPLA2, decreasing the expression of COX-2 and inhibiting the catalytic activities of 5-LOX. These activities may contribute to the antiinflammatory and anticarcinogenic actions of curcumin and its analogs.",
author = "Jungil Hong and Mousumi Bose and Jihyeung Ju and Ryu, {Jae Ha} and Xiaoxin Chen and Shengmin Sang and Lee, {Mao Jung} and Yang, {Chung S.}",
year = "2004",
month = "9",
day = "1",
doi = "10.1093/carcin/bgh165",
language = "English",
volume = "25",
pages = "1671--1679",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "9",

}

Modulation of arachidonic acid metabolism by curcumin and related β-diketone derivatives : Effects on cytosolic phospholipase A2, cyclooxygenases and 5-lipoxygenase. / Hong, Jungil; Bose, Mousumi; Ju, Jihyeung; Ryu, Jae Ha; Chen, Xiaoxin; Sang, Shengmin; Lee, Mao Jung; Yang, Chung S.

In: Carcinogenesis, Vol. 25, No. 9, 01.09.2004, p. 1671-1679.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Modulation of arachidonic acid metabolism by curcumin and related β-diketone derivatives

T2 - Effects on cytosolic phospholipase A2, cyclooxygenases and 5-lipoxygenase

AU - Hong, Jungil

AU - Bose, Mousumi

AU - Ju, Jihyeung

AU - Ryu, Jae Ha

AU - Chen, Xiaoxin

AU - Sang, Shengmin

AU - Lee, Mao Jung

AU - Yang, Chung S.

PY - 2004/9/1

Y1 - 2004/9/1

N2 - 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 β-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 A2 (cPLA2), cyclooxygenases (COX) as well as 5-lipoxygenase (5-LOX). At 10 μM, 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 cPLA2, the activation process of this enzyme, rather than direct inhibition of cPLA2 activity appears to be involved in the effect of curcumin. All the curcuminoids (10 μM) potently inhibited the formation of prostaglandin E2 (PGE2) in LPS-stimulated RAW cells. Curcumin (20 μM) significantly inhibited LPS-induced COX-2 expression; this effect, rather than the catalytic inhibition of COX, may contribute to the decreased PGE2 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 IC50 values of 0.7 and 3 μM, respectively. The results suggest that curcumin affects arachidonic acid metabolism by blocking the phosphorylation of cPLA2, decreasing the expression of COX-2 and inhibiting the catalytic activities of 5-LOX. These activities may contribute to the antiinflammatory and anticarcinogenic actions of curcumin and its analogs.

AB - 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 β-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 A2 (cPLA2), cyclooxygenases (COX) as well as 5-lipoxygenase (5-LOX). At 10 μM, 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 cPLA2, the activation process of this enzyme, rather than direct inhibition of cPLA2 activity appears to be involved in the effect of curcumin. All the curcuminoids (10 μM) potently inhibited the formation of prostaglandin E2 (PGE2) in LPS-stimulated RAW cells. Curcumin (20 μM) significantly inhibited LPS-induced COX-2 expression; this effect, rather than the catalytic inhibition of COX, may contribute to the decreased PGE2 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 IC50 values of 0.7 and 3 μM, respectively. The results suggest that curcumin affects arachidonic acid metabolism by blocking the phosphorylation of cPLA2, decreasing the expression of COX-2 and inhibiting the catalytic activities of 5-LOX. These activities may contribute to the antiinflammatory and anticarcinogenic actions of curcumin and its analogs.

UR - http://www.scopus.com/inward/record.url?scp=4544236324&partnerID=8YFLogxK

U2 - 10.1093/carcin/bgh165

DO - 10.1093/carcin/bgh165

M3 - Article

VL - 25

SP - 1671

EP - 1679

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 9

ER -