|
|
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result sql = Curcumin blocks prostaglandin E2 biosynthesis through direct inhibition of the microsomal prostaglandin E2 synthase-1.
Curcumin blocks prostaglandin E2 biosynthesis through direct inhibition of the microsomal prostaglandin E2 synthase-1.char = P;code = 80
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char = 2;code = 50
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char = e;code = 101
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char = a;code = 97
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char = a;code = 97
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char = l;code = 108
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char = m;code = 109
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char = L;code = 76
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char = C;code = 67
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char = l;code = 108
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char = a;code = 97
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char = .;code = 46
char = ,;code = 44
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char = a;code = 97
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char = t;code = 116
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char = i;code = 105
char = s;code = 115
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char = r;code = 114
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char = a;code = 97
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char = d;code = 100
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char = i;code = 105
char = n;code = 110
char = e;code = 101
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char = C;code = 67
char = O;code = 79
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char = -;code = 45
char = 1;code = 49
char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = a;code = 97
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char = c;code = 99
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char = b;code = 98
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = n;code = 110
char = t;code = 116
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char = C;code = 67
char = O;code = 79
char = X;code = 88
char = -;code = 45
char = 2;code = 50
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char = w;code = 119
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char = r;code = 114
char = e;code = 101
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char = e;code = 101
char = d;code = 100
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char = c;code = 99
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char = u;code = 117
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char = n;code = 110
char = ;code = 32
char = u;code = 117
char = p;code = 112
char = ;code = 32
char = t;code = 116
char = o;code = 111
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char = 3;code = 51
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char = c;code = 99
char = r;code = 114
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char = m;code = 109
char = o;code = 111
char = l;code = 108
char = /;code = 47
char = L;code = 76
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = p;code = 112
char = o;code = 111
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char = o;code = 111
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char = d;code = 100
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char = a;code = 97
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = O;code = 79
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char = 2;code = 50
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char = P;code = 80
char = G;code = 71
char = F;code = 70
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char = a;code = 97
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char = d;code = 100
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char = C;code = 67
char = O;code = 79
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char = 1;code = 49
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char = d;code = 100
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char = S;code = 83
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char = P;code = 80
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char = a;code = 97
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char = G;code = 71
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char = f;code = 102
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char = m;code = 109
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result sql = Prostaglandin E(2) (PGE(2)) plays a crucial role in the apparent link between tumor growth and chronic inflammation. Cyclooxygenase (COX)-2 and microsomal PGE(2) synthase-1, which are overexpressed in many cancers, are functionally coupled and thus produce massive PGE(2) in various tumors. Curcumin, a polyphenolic beta-diketone from tumeric with anti-carcinogenic and anti-inflammatory activities, was shown to suppress PGE(2) formation and to block the expression of COX-2 and of microsomal PGE(2) synthase-1. Here, we identified microsomal PGE(2) synthase-1 as a molecular target of curcumin and we show that inhibition of microsomal PGE(2) synthase-1 activity is the predominant mechanism of curcumin to suppress PGE(2) biosynthesis. Curcumin reversibly inhibited the conversion of PGH(2) to PGE(2) by microsomal PGE(2) synthase-1 in microsomes of interleukin-1beta-stimulated A549 lung carcinoma cells with an IC(50) of 0.2 to 0.3 micromol/L. Closely related polyphenols (e.g., resveratrol, coniferyl alcohol, eugenol, rosmarinic acid) failed in this respect, and isolated ovine COX-1 and human recombinant COX-2 were not inhibited by curcumin up to 30 micromol/L. In lipopolysaccharide-stimulated human whole blood, curcumin inhibited COX-2-derived PGE(2) formation from endogenous or from exogenous arachidonic acid, whereas the concomitant formation of COX-2-mediated 6-keto PGF(1)alpha and COX-1-derived 12(S)-hydroxy-5-cis-8,10-trans-heptadecatrienoic acid was suppressed only at significant higher concentrations. Based on the key function of PGE(2) in inflammation and carcinogenesis, inhibition of microsomal PGE(2) synthase-1 by curcumin provides a molecular basis for its anticarcinogenic and anti-inflammatory activities.
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result sql = Curcumin blocks prostaglandin E2 biosynthesis through direct inhibition of the microsomal prostaglandin E2 synthase-1.
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char = L;code = 76
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char = C;code = 67
char = O;code = 79
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char = C;code = 67
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result sql = Prostaglandin E(2) (PGE(2)) plays a crucial role in the apparent link between tumor growth and chronic inflammation. Cyclooxygenase (COX)-2 and microsomal PGE(2) synthase-1, which are overexpressed in many cancers, are functionally coupled and thus produce massive PGE(2) in various tumors. Curcumin, a polyphenolic beta-diketone from tumeric with anti-carcinogenic and anti-inflammatory activities, was shown to suppress PGE(2) formation and to block the expression of COX-2 and of microsomal PGE(2) synthase-1. Here, we identified microsomal PGE(2) synthase-1 as a molecular target of curcumin and we show that inhibition of microsomal PGE(2) synthase-1 activity is the predominant mechanism of curcumin to suppress PGE(2) biosynthesis. Curcumin reversibly inhibited the conversion of PGH(2) to PGE(2) by microsomal PGE(2) synthase-1 in microsomes of interleukin-1beta-stimulated A549 lung carcinoma cells with an IC(50) of 0.2 to 0.3 micromol/L. Closely related polyphenols (e.g., resveratrol, coniferyl alcohol, eugenol, rosmarinic acid) failed in this respect, and isolated ovine COX-1 and human recombinant COX-2 were not inhibited by curcumin up to 30 micromol/L. In lipopolysaccharide-stimulated human whole blood, curcumin inhibited COX-2-derived PGE(2) formation from endogenous or from exogenous arachidonic acid, whereas the concomitant formation of COX-2-mediated 6-keto PGF(1)alpha and COX-1-derived 12(S)-hydroxy-5-cis-8,10-trans-heptadecatrienoic acid was suppressed only at significant higher concentrations. Based on the key function of PGE(2) in inflammation and carcinogenesis, inhibition of microsomal PGE(2) synthase-1 by curcumin provides a molecular basis for its anticarcinogenic and anti-inflammatory activities.
Publication: Mol. Cancer Ther. 2009 Aug ;8(8)::2348-55. :doi: 10.1158/1535-7163.MCT-09-0290.
Publication Date: 2009 Aug
Study Author(s): Koeberle, Andreas;Northoff, Hinnak;Werz, Oliver;
Institution: Department of Pharmaceutical Analytics, Pharmaceutical Institute, University of Tuebingen, D-72076 Tuebingen, Germany.
Shortcut link to this study:
Publication Date: 2009 Aug
Study Author(s): Koeberle, Andreas;Northoff, Hinnak;Werz, Oliver;
Institution: Department of Pharmaceutical Analytics, Pharmaceutical Institute, University of Tuebingen, D-72076 Tuebingen, Germany.
Shortcut link to this study:
Prostaglandin E(2) (PGE(2)) plays a crucial role in the apparent link between tumor growth and chronic inflammation. Cyclooxygenase (COX)-2 and microsomal PGE(2) synthase-1, which are overexpressed in many cancers, are functionally coupled and thus produce massive PGE(2) in various tumors. Curcumin, a polyphenolic beta-diketone from tumeric with anti-carcinogenic and anti-inflammatory activities, was shown to suppress PGE(2) formation and to block the expression of COX-2 and of microsomal PGE(2) synthase-1. Here, we identified microsomal PGE(2) synthase-1 as a molecular target of curcumin and we show that inhibition of microsomal PGE(2) synthase-1 activity is the predominant mechanism of curcumin to suppress PGE(2) biosynthesis. Curcumin reversibly inhibited the conversion of PGH(2) to PGE(2) by microsomal PGE(2) synthase-1 in microsomes of interleukin-1beta-stimulated A549 lung carcinoma cells with an IC(50) of 0.2 to 0.3 micromol/L. Closely related polyphenols (e.g., resveratrol, coniferyl alcohol, eugenol, rosmarinic acid) failed in this respect, and isolated ovine COX-1 and human recombinant COX-2 were not inhibited by curcumin up to 30 micromol/L. In lipopolysaccharide-stimulated human whole blood, curcumin inhibited COX-2-derived PGE(2) formation from endogenous or from exogenous arachidonic acid, whereas the concomitant formation of COX-2-mediated 6-keto PGF(1)alpha and COX-1-derived 12(S)-hydroxy-5-cis-8,10-trans-heptadecatrienoic acid was suppressed only at significant higher concentrations. Based on the key function of PGE(2) in inflammation and carcinogenesis, inhibition of microsomal PGE(2) synthase-1 by curcumin provides a molecular basis for its anticarcinogenic and anti-inflammatory activities.
PMID: 19671757
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