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char = o;code = 111
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char = m;code = 109
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char = a;code = 97
char = g;code = 103
char = o;code = 111
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char = z;code = 122
char = e;code = 101
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char = a;code = 97
char = c;code = 99
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char = i;code = 105
char = v;code = 118
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char = t;code = 116
char = o;code = 111
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char = r;code = 114
char = o;code = 111
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char = d;code = 100
char = e;code = 101
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char = t;code = 116
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char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = o;code = 111
char = o;code = 111
char = x;code = 120
char = y;code = 121
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = e;code = 101
char = x;code = 120
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char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = h;code = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = n;code = 110
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = .;code = 46
result sql = Rosmarinic acid antagonizes activator protein-1-dependent activation of cyclooxygenase-2 expression in human cancer and nonmalignant cell lines.
Rosmarinic acid antagonizes activator protein-1-dependent activation of cyclooxygenase-2 expression in human cancer and nonmalignant cell lines.
char = O;code = 79
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char = ;code = 32
char = m;code = 109
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char = c;code = 99
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char = a;code = 97
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = b;code = 98
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char = o;code = 111
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char = v;code = 118
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char = d;code = 100
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = o;code = 111
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char = e;code = 101
char = n;code = 110
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char = s;code = 115
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = y;code = 121
char = ;code = 32
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char = x;code = 120
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char = ;code = 32
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char = f;code = 102
char = e;code = 101
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char = s;code = 115
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char = s;code = 115
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char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
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char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
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char = o;code = 111
char = i;code = 105
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char = f;code = 102
char = l;code = 108
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char = m;code = 109
char = a;code = 97
char = t;code = 116
char = o;code = 111
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char = y;code = 121
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = o;code = 111
char = o;code = 111
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char = e;code = 101
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char = c;code = 99
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char = h;code = 104
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char = b;code = 98
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char = e;code = 101
char = n;code = 110
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char = r;code = 114
char = e;code = 101
char = g;code = 103
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char = e;code = 101
char = d;code = 100
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char = ;code = 32
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char = i;code = 105
char = s;code = 115
char = k;code = 107
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = c;code = 99
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char = o;code = 111
char = r;code = 114
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char = ;code = 32
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char = u;code = 117
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char = p;code = 112
char = m;code = 109
char = e;code = 101
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char = t;code = 116
char = .;code = 46
char = ;code = 32
char = R;code = 82
char = o;code = 111
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char = a;code = 97
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char = a;code = 97
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char = i;code = 105
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char = f;code = 102
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char = a;code = 97
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char = i;code = 105
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char = m;code = 109
char = a;code = 97
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char = ;code = 32
char = (;code = 40
char = R;code = 82
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char = m;code = 109
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = n;code = 110
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char = s;code = 115
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char = o;code = 111
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char = f;code = 102
char = i;code = 105
char = c;code = 99
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char = a;code = 97
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char = s;code = 115
char = ;code = 32
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char = e;code = 101
char = a;code = 97
char = r;code = 114
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char = ;code = 32
char = d;code = 100
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char = u;code = 117
char = m;code = 109
char = e;code = 101
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = R;code = 82
char = A;code = 65
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = y;code = 121
char = ;code = 32
char = e;code = 101
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char = ;code = 32
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char = t;code = 116
char = i;code = 105
char = i;code = 105
char = n;code = 110
char = f;code = 102
char = l;code = 108
char = a;code = 97
char = m;code = 109
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = o;code = 111
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char = y;code = 121
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char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
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char = s;code = 115
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = v;code = 118
char = e;code = 101
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char = ,;code = 44
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char = e;code = 101
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char = m;code = 109
char = s;code = 115
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char = a;code = 97
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char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = R;code = 82
char = A;code = 65
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = C;code = 67
char = O;code = 79
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char = b;code = 98
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char = H;code = 72
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char = c;code = 99
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char = T;code = 84
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char = (;code = 40
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char = .;code = 46
char = ;code = 32
char = I;code = 73
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char = 0;code = 48
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char = ;code = 32
char = <;code = 60
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char = 0;code = 48
char = 1;code = 49
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char = ;code = 32
char = T;code = 84
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char = l;code = 108
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char = r;code = 114
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char = s;code = 115
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char = t;code = 116
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char = e;code = 101
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char = f;code = 102
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char = J;code = 74
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char = m;code = 109
char = o;code = 111
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char = /;code = 47
char = L;code = 76
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char = P;code = 80
char = ;code = 32
char = <;code = 60
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char = 1;code = 49
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char = a;code = 97
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char = c;code = 99
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char = F;code = 70
char = o;code = 111
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char = (;code = 40
char = 1;code = 49
char = 0;code = 48
char = ;code = 32
char = m;code = 109
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char = c;code = 99
char = r;code = 114
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char = m;code = 109
char = o;code = 111
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char = /;code = 47
char = L;code = 76
char = ;;code = 59
char = ;code = 32
char = P;code = 80
char = ;code = 32
char = <;code = 60
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char = 0;code = 48
char = .;code = 46
char = 0;code = 48
char = 5;code = 53
char = );code = 41
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = C;code = 67
char = O;code = 79
char = X;code = 88
char = -;code = 45
char = 2;code = 50
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char = p;code = 112
char = r;code = 114
char = o;code = 111
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char = h;code = 104
char = a;code = 97
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char = b;code = 98
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char = r;code = 114
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char = n;code = 110
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char = a;code = 97
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char = c;code = 99
char = A;code = 65
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char = P;code = 80
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char = o;code = 111
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char = e;code = 101
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char = e;code = 101
char = l;code = 108
char = e;code = 101
char = m;code = 109
char = e;code = 101
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char = t;code = 116
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char = (;code = 40
char = C;code = 67
char = R;code = 82
char = E;code = 69
char = );code = 41
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
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char = a;code = 97
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char = A;code = 65
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char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = s;code = 115
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = R;code = 82
char = A;code = 65
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
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char = ;code = 32
char = n;code = 110
char = o;code = 111
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char = i;code = 105
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char = a;code = 97
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char = b;code = 98
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char = l;code = 108
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char = l;code = 108
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char = h;code = 104
char = i;code = 105
char = c;code = 99
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char = R;code = 82
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char = ;code = 32
char = a;code = 97
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char = t;code = 116
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char = l;code = 108
char = a;code = 97
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char = y;code = 121
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char = f;code = 102
char = f;code = 102
char = e;code = 101
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char = t;code = 116
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char = ;code = 32
char = T;code = 84
char = P;code = 80
char = A;code = 65
char = ;code = 32
char = o;code = 111
char = n;code = 110
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char = C;code = 67
char = O;code = 79
char = X;code = 88
char = -;code = 45
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char = t;code = 116
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char = L;code = 76
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char = ;code = 32
char = P;code = 80
char = ;code = 32
char = <;code = 60
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char = 0;code = 48
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char = P;code = 80
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char = a;code = 97
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char = m;code = 109
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char = L;code = 76
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char = P;code = 80
char = ;code = 32
char = <;code = 60
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char = C;code = 67
char = O;code = 79
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char = R;code = 82
char = E;code = 69
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char = E;code = 69
char = R;code = 82
char = K;code = 75
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char = L;code = 76
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char = a;code = 97
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char = l;code = 108
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char = R;code = 82
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char = a;code = 97
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char = t;code = 116
char = a;code = 97
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char = i;code = 105
char = z;code = 122
char = e;code = 101
char = d;code = 100
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char = E;code = 69
char = R;code = 82
char = K;code = 75
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char = 2;code = 50
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char = a;code = 97
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char = H;code = 72
char = T;code = 84
char = -;code = 45
char = 2;code = 50
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char = a;code = 97
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char = e;code = 101
char = a;code = 97
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char = M;code = 77
char = C;code = 67
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char = -;code = 45
char = 7;code = 55
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char = m;code = 109
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char = c;code = 99
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result sql = One mechanism through which bioactive food components may exert anticancer effects is by reducing the expression of the proinflammatory gene cyclooxygenase-2 (COX-2), which has been regarded as a risk factor in tumor development. Rosmarinic acid (RA) is a phenolic derivative of caffeic acid present in rosemary (Rosmarinus officinalis). Previous research documented that RA may exert antiinflammatory effects. However, the mechanisms of action of RA on COX-2 expression have not been investigated. Here, we report that in colon cancer HT-29 cells, RA (5, 10, and 20 micromol/L) reduced the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced COX-2 promoter activity (P < 0.05) and protein levels (P < 0.05). In addition, the cotreatment with RA reduced (5 micromol/L, P < 0.05; 10 and 20 micromol/L, P < 0.01) TPA-induced transcription from a control activator protein-1 (AP-1) promoter-luciferase construct and repressed binding of the AP-1 factors c-Jun (10 micromol/L; P < 0.01) and c-Fos (10 micromol/L; P < 0.05) to COX-2 promoter oligonucleotides harboring a cAMP-response element (CRE). The anti-AP1 effects of RA were also examined in a nonmalignant breast epithelial cell line (MCF10A) in which RA antagonized the stimulatory effects of TPA on COX-2 protein expression (5 micromol/L, P < 0.05; 10 and 20 micromol/L, P < 0.01), the recruitment of c-Jun and c-Fos (10 micromol/L; P < 0.01) to the COX-2/CRE oligonucleotides, and activation of the extracellular signal-regulated protein kinase-1/2 (ERK1/2) (10 micromol/L; P < 0.01), a member of the mitogen-activated protein kinase pathway. Additionally, RA antagonized ERK1/2 activation in colon HT-29 and breast MCF-7 cancer cells (10 micromol/L; P < 0.01). Thus, we propose that RA may be an effective preventative agent against COX-2 activation by AP-1-inducing agents in both cancer and nonmalignant mammary epithelial cells.

Publication: J. Nutr. 2008 Nov ;138(11)::2098-105. :doi: 10.3945/jn.108.090431.
Publication Date: 2008 Nov
Study Author(s): Scheckel, Kristen A;Degner, Stephanie C;Romagnolo, Donato F;
Institution: Department of Nutritional Sciences, University of Arizona, Tucson, AZ 85718, USA.
Shortcut link to this study:
One mechanism through which bioactive food components may exert anticancer effects is by reducing the expression of the proinflammatory gene cyclooxygenase-2 (COX-2), which has been regarded as a risk factor in tumor development. Rosmarinic acid (RA) is a phenolic derivative of caffeic acid present in rosemary (Rosmarinus officinalis). Previous research documented that RA may exert antiinflammatory effects. However, the mechanisms of action of RA on COX-2 expression have not been investigated. Here, we report that in colon cancer HT-29 cells, RA (5, 10, and 20 micromol/L) reduced the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced COX-2 promoter activity (P < 0.05) and protein levels (P < 0.05). In addition, the cotreatment with RA reduced (5 micromol/L, P < 0.05; 10 and 20 micromol/L, P < 0.01) TPA-induced transcription from a control activator protein-1 (AP-1) promoter-luciferase construct and repressed binding of the AP-1 factors c-Jun (10 micromol/L; P < 0.01) and c-Fos (10 micromol/L; P < 0.05) to COX-2 promoter oligonucleotides harboring a cAMP-response element (CRE). The anti-AP1 effects of RA were also examined in a nonmalignant breast epithelial cell line (MCF10A) in which RA antagonized the stimulatory effects of TPA on COX-2 protein expression (5 micromol/L, P < 0.05; 10 and 20 micromol/L, P < 0.01), the recruitment of c-Jun and c-Fos (10 micromol/L; P < 0.01) to the COX-2/CRE oligonucleotides, and activation of the extracellular signal-regulated protein kinase-1/2 (ERK1/2) (10 micromol/L; P < 0.01), a member of the mitogen-activated protein kinase pathway. Additionally, RA antagonized ERK1/2 activation in colon HT-29 and breast MCF-7 cancer cells (10 micromol/L; P < 0.01). Thus, we propose that RA may be an effective preventative agent against COX-2 activation by AP-1-inducing agents in both cancer and nonmalignant mammary epithelial cells.
PMID: 18936204

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