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result sql = Resveratrol activates adenylyl-cyclase in human breast cancer cells: a novel, estrogen receptor-independent cytostatic mechanism.
Resveratrol activates adenylyl-cyclase in human breast cancer cells: a novel, estrogen receptor-independent cytostatic mechanism.
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char = ;code = 32
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char = P;code = 80
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char = E;code = 69
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char = ;code = 32
char = i;code = 105
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char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
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char = (;code = 40
char = I;code = 73
char = B;code = 66
char = M;code = 77
char = X;code = 88
char = ,;code = 44
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 5;code = 53
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char = m;code = 109
char = M;code = 77
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char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = A;code = 65
char = M;code = 77
char = P;code = 80
char = -;code = 45
char = s;code = 115
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char = e;code = 101
char = c;code = 99
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = P;code = 80
char = D;code = 68
char = E;code = 69
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
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char = r;code = 114
char = ;code = 32
char = (;code = 40
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = p;code = 112
char = r;code = 114
char = a;code = 97
char = m;code = 109
char = ,;code = 44
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char = 1;code = 49
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
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char = ;code = 32
char = M;code = 77
char = );code = 41
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
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char = e;code = 101
char = a;code = 97
char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = t;code = 116
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char = e;code = 101
char = s;code = 115
char = e;code = 101
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char = P;code = 80
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char = E;code = 69
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char = i;code = 105
char = n;code = 110
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char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
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char = r;code = 114
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
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char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
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char = l;code = 108
char = y;code = 121
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char = a;code = 97
char = u;code = 117
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char = e;code = 101
char = n;code = 110
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char = d;code = 100
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char = m;code = 109
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char = x;code = 120
char = i;code = 105
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = A;code = 65
char = M;code = 77
char = P;code = 80
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = R;code = 82
char = S;code = 83
char = V;code = 86
char = L;code = 76
char = .;code = 46
char = ;code = 32
char = P;code = 80
char = a;code = 97
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
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char = r;code = 114
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
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 = e;code = 101
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = R;code = 82
char = S;code = 83
char = V;code = 86
char = L;code = 76
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = p;code = 112
char = r;code = 114
char = a;code = 97
char = m;code = 109
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char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = f;code = 102
char = e;code = 101
char = r;code = 114
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 = t;code = 116
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
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char = i;code = 105
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char = ;code = 32
char = a;code = 97
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char = c;code = 99
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = -;code = 45
char = r;code = 114
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char = s;code = 115
char = p;code = 112
char = o;code = 111
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char = s;code = 115
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char = v;code = 118
char = e;code = 101
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char = m;code = 109
char = a;code = 97
char = n;code = 110
char = n;code = 110
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char = r;code = 114
char = .;code = 46
char = ;code = 32
char = F;code = 70
char = u;code = 117
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = u;code = 117
char = r;code = 114
char = r;code = 114
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char = n;code = 110
char = t;code = 116
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char = t;code = 116
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char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
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char = n;code = 110
char = t;code = 116
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = R;code = 82
char = S;code = 83
char = V;code = 86
char = L;code = 76
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = r;code = 114
char = o;code = 111
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char = i;code = 105
char = p;code = 112
char = r;code = 114
char = a;code = 97
char = m;code = 109
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
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char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = l;code = 108
char = y;code = 121
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char = e;code = 101
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char = h;code = 104
char = a;code = 97
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char = c;code = 99
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char = t;code = 116
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char = e;code = 101
char = i;code = 105
char = r;code = 114
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char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
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char = i;code = 105
char = d;code = 100
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char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
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char = t;code = 116
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char = t;code = 116
char = o;code = 111
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char = c;code = 99
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char = e;code = 101
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char = n;code = 110
char = s;code = 115
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char = s;code = 115
char = .;code = 46
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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 = t;code = 116
char = i;code = 105
char = p;code = 112
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char = i;code = 105
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = a;code = 97
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char = i;code = 105
char = v;code = 118
char = e;code = 101
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char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
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char = t;code = 116
char = s;code = 115
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char = e;code = 101
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char = p;code = 112
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char = a;code = 97
char = b;code = 98
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char = e;code = 101
char = r;code = 114
char = s;code = 115
char = e;code = 101
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char = b;code = 98
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char = t;code = 116
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char = e;code = 101
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char = k;code = 107
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = -;code = 45
char = A;code = 65
char = ;code = 32
char = i;code = 105
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char = i;code = 105
char = b;code = 98
char = i;code = 105
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char = o;code = 111
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char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = R;code = 82
char = p;code = 112
char = -;code = 45
char = c;code = 99
char = A;code = 65
char = M;code = 77
char = P;code = 80
char = S;code = 83
char = ;code = 32
char = (;code = 40
char = 1;code = 49
char = 0;code = 48
char = 0;code = 48
char = -;code = 45
char = 3;code = 51
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char = 0;code = 48
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char = i;code = 105
char = c;code = 99
char = r;code = 114
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char = M;code = 77
char = );code = 41
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = K;code = 75
char = T;code = 84
char = -;code = 45
char = 5;code = 53
char = 7;code = 55
char = 2;code = 50
char = 0;code = 48
char = ;code = 32
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char = 1;code = 49
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char = m;code = 109
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char = c;code = 99
char = r;code = 114
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char = M;code = 77
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char = .;code = 46
char = ;code = 32
char = P;code = 80
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char = e;code = 101
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char = t;code = 116
char = h;code = 104
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = c;code = 99
char = P;code = 80
char = L;code = 76
char = A;code = 65
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char = r;code = 114
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char = a;code = 97
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char = y;code = 121
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char = f;code = 102
char = l;code = 108
char = u;code = 117
char = o;code = 111
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char = o;code = 111
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char = y;code = 121
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char = k;code = 107
char = e;code = 101
char = t;code = 116
char = o;code = 111
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char = 1;code = 49
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char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
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char = z;code = 122
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char = f;code = 102
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char = t;code = 116
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char = R;code = 82
char = S;code = 83
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char = L;code = 76
char = ,;code = 44
char = ;code = 32
char = b;code = 98
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char = f;code = 102
char = e;code = 101
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char = a;code = 97
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char = p;code = 112
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char = A;code = 65
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char = e;code = 101
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char = h;code = 104
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char = a;code = 97
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char = f;code = 102
char = o;code = 111
char = r;code = 114
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char = t;code = 116
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char = e;code = 101
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char = f;code = 102
char = i;code = 105
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char = t;code = 116
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char = a;code = 97
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char = t;code = 116
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char = e;code = 101
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char = c;code = 99
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char = e;code = 101
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char = a;code = 97
char = p;code = 112
char = e;code = 101
char = u;code = 117
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char = i;code = 105
char = c;code = 99
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char = a;code = 97
char = g;code = 103
char = e;code = 101
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char = t;code = 116
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char = R;code = 82
char = S;code = 83
char = V;code = 86
char = L;code = 76
char = ;code = 32
char = i;code = 105
char = s;code = 115
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char = a;code = 97
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char = o;code = 111
char = n;code = 110
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char = s;code = 115
char = t;code = 116
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char = f;code = 102
char = o;code = 111
char = r;code = 114
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = c;code = 99
char = A;code = 65
char = M;code = 77
char = P;code = 80
char = /;code = 47
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = -;code = 45
char = A;code = 65
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char = s;code = 115
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char = s;code = 115
char = t;code = 116
char = e;code = 101
char = m;code = 109
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char = d;code = 100
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char = e;code = 101
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char = e;code = 101
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char = a;code = 97
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char = o;code = 111
char = p;code = 112
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char = i;code = 105
char = c;code = 99
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char = d;code = 100
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
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result sql = Resveratrol (RSVL) is a well-established chemopreventive agent in human breast cancer models. The molecular basis of its action is far less characterized. We investigated the effects of RSVL on activity of adenylate- and guanylate-cyclase (AC, GC) enzymes; two known cytostatic cascades in MCF-7 breast cancer cells RSVL : increased cAMP levels in both time- and concentration-dependent manners (t(1/2), 6.2 min; EC(50) 0.8 micro M). In contrast, it had no effect on cGMP levels. The stimulatory effects for RSVL on AC were not altered either by the protein synthesis inhibitor (actinomycin-D, 5 micro M) or the estrogen-receptor (ER) blockers (tamoxifen and ICI182,780, 1 micro M each). Likewise, cAMP formation by RSVL was insensitive to either the broad-spectrum phosphodiesterase (PDE) inhibitor (IBMX, 0.5 mM) or the cAMP-specific PDE inhibitor (rolipram, 10 micro M). Instead, these PDE inhibitors significantly augmented maximal cAMP formation by RSVL. Parallel experiments showed that either RSVL or rolipram inhibited the proliferation of these cells in a concentration-responsive manner. Further, concurrent treatment with RSVL and rolipram significantly enhanced their individual cytotoxic responses. The antiproliferative effects were appreciably reversed by the kinase-A inhibitors, Rp-cAMPS (100-300 micro M) or KT-5720 (10 micro M). Pretreatment with the cPLA(2) inhibitor arachidonyl trifluoromethyl ketone (10 micro M) markedly antagonized the cytotoxic effects of RSVL, but had no effect on that of rolipram. Altogether, the present study demonstrates, for the first time, that the chemotherapeutic agent RSVL is an agonist for the cAMP/kinase-A system, a documented pro-apoptic and cell-cycle suppressor in breast cancer cells.

Publication: Carcinogenesis 2003 May ;24(5)::869-73.
Publication Date: 2003 May
Study Author(s): El-Mowafy, Abdalla M;Alkhalaf, Moussa;
Institution: Department of Applied Therapeutics, Faculty of Pharmacy, Health Sciences Center, Kuwait University, PO Box 24923, Safat 13110, Kuwait. [email protected]
Shortcut link to this study:
Resveratrol (RSVL) is a well-established chemopreventive agent in human breast cancer models. The molecular basis of its action is far less characterized. We investigated the effects of RSVL on activity of adenylate- and guanylate-cyclase (AC, GC) enzymes; two known cytostatic cascades in MCF-7 breast cancer cells RSVL : increased cAMP levels in both time- and concentration-dependent manners (t(1/2), 6.2 min; EC(50) 0.8 micro M). In contrast, it had no effect on cGMP levels. The stimulatory effects for RSVL on AC were not altered either by the protein synthesis inhibitor (actinomycin-D, 5 micro M) or the estrogen-receptor (ER) blockers (tamoxifen and ICI182,780, 1 micro M each). Likewise, cAMP formation by RSVL was insensitive to either the broad-spectrum phosphodiesterase (PDE) inhibitor (IBMX, 0.5 mM) or the cAMP-specific PDE inhibitor (rolipram, 10 micro M). Instead, these PDE inhibitors significantly augmented maximal cAMP formation by RSVL. Parallel experiments showed that either RSVL or rolipram inhibited the proliferation of these cells in a concentration-responsive manner. Further, concurrent treatment with RSVL and rolipram significantly enhanced their individual cytotoxic responses. The antiproliferative effects were appreciably reversed by the kinase-A inhibitors, Rp-cAMPS (100-300 micro M) or KT-5720 (10 micro M). Pretreatment with the cPLA(2) inhibitor arachidonyl trifluoromethyl ketone (10 micro M) markedly antagonized the cytotoxic effects of RSVL, but had no effect on that of rolipram. Altogether, the present study demonstrates, for the first time, that the chemotherapeutic agent RSVL is an agonist for the cAMP/kinase-A system, a documented pro-apoptic and cell-cycle suppressor in breast cancer cells.
PMID: 12771030

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