|
|
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result sql = A methoxy derivative of resveratrol analogue selectively induced activation of the mitochondrial apoptotic pathway in transformed fibroblasts.
A methoxy derivative of resveratrol analogue selectively induced activation of the mitochondrial apoptotic pathway in transformed fibroblasts.char = R;code = 82
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char = I;code = 73
char = C;code = 67
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char = a;code = 97
char = l;code = 108
char = u;code = 117
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char = o;code = 111
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char = 3;code = 51
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char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = W;code = 87
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char = V;code = 86
char = A;code = 65
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 = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = o;code = 111
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char = t;code = 116
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char = 5;code = 53
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 = M;code = 77
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char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
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 = 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
char = t;code = 116
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = M;code = 77
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char = -;code = 45
char = 4;code = 52
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
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 = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = h;code = 104
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = W;code = 87
char = I;code = 73
char = 3;code = 51
char = 8;code = 56
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 = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = W;code = 87
char = I;code = 73
char = 3;code = 51
char = 8;code = 56
char = V;code = 86
char = A;code = 65
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 = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = M;code = 77
char = R;code = 82
char = -;code = 45
char = 4;code = 52
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = s;code = 115
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 = ;code = 32
char = B;code = 66
char = a;code = 97
char = x;code = 120
char = /;code = 47
char = B;code = 66
char = c;code = 99
char = l;code = 108
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = m;code = 109
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = ,;code = 44
char = ;code = 32
char = p;code = 112
char = 5;code = 53
char = 3;code = 51
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = B;code = 66
char = a;code = 97
char = x;code = 120
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = ,;code = 44
char = ;code = 32
char = a;code = 97
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 = a;code = 97
char = s;code = 115
char = p;code = 112
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = D;code = 68
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = a;code = 97
char = g;code = 103
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = b;code = 98
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char = t;code = 116
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char = t;code = 116
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = n;code = 110
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char = r;code = 114
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
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char = l;code = 108
char = s;code = 115
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char = u;code = 117
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
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char = a;code = 97
char = l;code = 108
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char = s;code = 115
char = i;code = 105
char = s;code = 115
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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
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char = M;code = 77
char = R;code = 82
char = -;code = 45
char = 4;code = 52
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
char = e;code = 101
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char = ;code = 32
char = a;code = 97
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char = r;code = 114
char = a;code = 97
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char = i;code = 105
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char = ;code = 32
char = a;code = 97
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char = p;code = 112
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = a;code = 97
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char = c;code = 99
char = e;code = 101
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
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char = r;code = 114
char = i;code = 105
char = n;code = 110
char = u;code = 117
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = a;code = 97
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char = g;code = 103
char = r;code = 114
char = e;code = 101
char = g;code = 103
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 = m;code = 109
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = c;code = 99
char = h;code = 104
char = o;code = 111
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char = d;code = 100
char = r;code = 114
char = i;code = 105
char = a;code = 97
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = W;code = 87
char = I;code = 73
char = 3;code = 51
char = 8;code = 56
char = V;code = 86
char = A;code = 65
char = ;code = 32
char = b;code = 98
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char = t;code = 116
char = ;code = 32
char = n;code = 110
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char = t;code = 116
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = W;code = 87
char = I;code = 73
char = 3;code = 51
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char = ;code = 32
char = c;code = 99
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char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = g;code = 103
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = i;code = 105
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
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char = t;code = 116
char = h;code = 104
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char = m;code = 109
char = i;code = 105
char = t;code = 116
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char = d;code = 100
char = r;code = 114
char = i;code = 105
char = a;code = 97
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char = c;code = 99
char = o;code = 111
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char = l;code = 108
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = r;code = 114
char = v;code = 118
char = e;code = 101
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char = s;code = 115
char = ;code = 32
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char = ;code = 32
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = l;code = 108
char = y;code = 121
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char = t;code = 116
char = a;code = 97
char = r;code = 114
char = g;code = 103
char = e;code = 101
char = t;code = 116
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = M;code = 77
char = R;code = 82
char = -;code = 45
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char = .;code = 46
char = ;code = 32
char = R;code = 82
char = -;code = 45
char = 3;code = 51
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = o;code = 111
char = ;code = 32
char = i;code = 105
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char = u;code = 117
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char = ;code = 32
char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
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char = i;code = 105
char = s;code = 115
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char = a;code = 97
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char = d;code = 100
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char = m;code = 109
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char = t;code = 116
char = o;code = 111
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char = r;code = 114
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char = a;code = 97
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char = c;code = 99
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char = u;code = 117
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = r;code = 114
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char = b;code = 98
char = u;code = 117
char = t;code = 116
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char = l;code = 108
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char = a;code = 97
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char = c;code = 99
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char = h;code = 104
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char = s;code = 115
char = e;code = 101
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char = t;code = 116
char = o;code = 111
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char = 5;code = 53
char = 0;code = 48
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 = 46
char = ;code = 32
char = T;code = 84
char = a;code = 97
char = k;code = 107
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char = h;code = 104
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char = h;code = 104
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char = s;code = 115
char = p;code = 112
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char = c;code = 99
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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 = a;code = 97
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char = o;code = 111
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char = o;code = 111
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char = i;code = 105
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char = w;code = 119
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char = l;code = 108
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char = b;code = 98
char = e;code = 101
char = ;code = 32
char = a;code = 97
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char = m;code = 109
char = a;code = 97
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char = r;code = 114
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char = a;code = 97
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char = f;code = 102
char = o;code = 111
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = s;code = 115
char = t;code = 116
char = r;code = 114
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char = k;code = 107
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char = n;code = 110
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char = d;code = 100
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char = f;code = 102
char = f;code = 102
char = e;code = 101
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char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
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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
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
char = t;code = 116
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = M;code = 77
char = R;code = 82
char = -;code = 45
char = 4;code = 52
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
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result sql = Resveratrol (R-3), a trihydroxy trans-stilbene from grape, inhibits multistage carcinogenesis in animal models. A resveratrol derivative 3,4,5,4'-tetrahydroxystilbene (R-4) exhibits potent growth inhibitory effect against transformed human cells. Here we report that 3,4,5,4'-tetramethoxystilbene (MR-4), converted from R-4, was more potent against cancer cell lines (WI38VA, IMR-90SV, HeLa, LNCaP, HT-29, and HepG2), but had almost no inhibitory effect on the growth of normal cells (WI38, IMR-90, BJ-T) at the concentrations tested. The IC50 value of MR-4 on the growth inhibition of transformed WI38VA human cells was 0.5 microM, as compared to the value of greater than 50 microM for the normal WI38 cells. Resveratrol, however, did not exhibit such clear differential effect and the IC50 value of R-3 for WI38VA cells was about 50 microM. The growth inhibitory effect of MR-4 correlated with the induction of apoptosis in the transformed cells. When normal WI38 cells and transformed WI38VA cells were compared, MR-4 induced increases of the Bax/Bcl-2 mRNA ratio, p53 and Bax protein level, activation of caspases, and DNA fragmentation in transformed, but not in normal cells. Further analysis revealed that MR-4 caused a rapid appearance of perinuclear aggregation of mitochondria in WI38VA but not in WI38 cells, suggesting that the mitochondria could serve as an early target of MR-4. R-3 also induced apoptosis and mitochondrial clustering but only at a much higher concentration, close to 500 microM. Taken together, the specific activation of the mitochondria-mediated apoptotic pathway could be a major reason for the striking differential growth inhibitory effect of MR-4.
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result sql = A methoxy derivative of resveratrol analogue selectively induced activation of the mitochondrial apoptotic pathway in transformed fibroblasts.
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char = f;code = 102
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char = a;code = 97
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char = f;code = 102
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char = a;code = 97
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char = ;code = 32
char = t;code = 116
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char = I;code = 73
char = C;code = 67
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char = v;code = 118
char = a;code = 97
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char = u;code = 117
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char = o;code = 111
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char = ;code = 32
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char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = W;code = 87
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char = 3;code = 51
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char = V;code = 86
char = A;code = 65
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char = c;code = 99
char = e;code = 101
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char = l;code = 108
char = s;code = 115
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char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = o;code = 111
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char = t;code = 116
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char = 5;code = 53
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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 = T;code = 84
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char = e;code = 101
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char = g;code = 103
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char = o;code = 111
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char = i;code = 105
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char = t;code = 116
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char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
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char = o;code = 111
char = f;code = 102
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char = M;code = 77
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char = -;code = 45
char = 4;code = 52
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char = c;code = 99
char = o;code = 111
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char = r;code = 114
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char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
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char = t;code = 116
char = h;code = 104
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = u;code = 117
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char = o;code = 111
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char = o;code = 111
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char = ;code = 32
char = a;code = 97
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char = o;code = 111
char = p;code = 112
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char = o;code = 111
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char = s;code = 115
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
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char = e;code = 101
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char = t;code = 116
char = r;code = 114
char = a;code = 97
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char = s;code = 115
char = f;code = 102
char = o;code = 111
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char = e;code = 101
char = d;code = 100
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 = ;code = 32
char = W;code = 87
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char = e;code = 101
char = n;code = 110
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = W;code = 87
char = I;code = 73
char = 3;code = 51
char = 8;code = 56
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 = a;code = 97
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char = d;code = 100
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = W;code = 87
char = I;code = 73
char = 3;code = 51
char = 8;code = 56
char = V;code = 86
char = A;code = 65
char = ;code = 32
char = c;code = 99
char = e;code = 101
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char = l;code = 108
char = s;code = 115
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char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
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char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = M;code = 77
char = R;code = 82
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char = 4;code = 52
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
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char = e;code = 101
char = d;code = 100
char = ;code = 32
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char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = s;code = 115
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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
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char = B;code = 66
char = a;code = 97
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char = B;code = 66
char = c;code = 99
char = l;code = 108
char = -;code = 45
char = 2;code = 50
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char = m;code = 109
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char = N;code = 78
char = A;code = 65
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char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = ;code = 32
char = p;code = 112
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char = 3;code = 51
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = B;code = 66
char = a;code = 97
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char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
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char = n;code = 110
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char = v;code = 118
char = e;code = 101
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char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = c;code = 99
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char = i;code = 105
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char = a;code = 97
char = t;code = 116
char = i;code = 105
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char = n;code = 110
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char = o;code = 111
char = f;code = 102
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char = c;code = 99
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char = s;code = 115
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char = ,;code = 44
char = ;code = 32
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char = d;code = 100
char = ;code = 32
char = D;code = 68
char = N;code = 78
char = A;code = 65
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char = f;code = 102
char = r;code = 114
char = a;code = 97
char = g;code = 103
char = m;code = 109
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char = o;code = 111
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char = a;code = 97
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char = s;code = 115
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char = o;code = 111
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char = m;code = 109
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char = b;code = 98
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char = t;code = 116
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char = t;code = 116
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char = n;code = 110
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char = r;code = 114
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char = a;code = 97
char = l;code = 108
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char = c;code = 99
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char = l;code = 108
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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
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char = a;code = 97
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char = a;code = 97
char = l;code = 108
char = y;code = 121
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char = s;code = 115
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char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
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char = M;code = 77
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char = -;code = 45
char = 4;code = 52
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
char = e;code = 101
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char = r;code = 114
char = a;code = 97
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char = i;code = 105
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char = e;code = 101
char = a;code = 97
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char = a;code = 97
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char = ;code = 32
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char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
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char = a;code = 97
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char = g;code = 103
char = r;code = 114
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char = a;code = 97
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char = t;code = 116
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char = a;code = 97
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char = i;code = 105
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char = W;code = 87
char = I;code = 73
char = 3;code = 51
char = 8;code = 56
char = V;code = 86
char = A;code = 65
char = ;code = 32
char = b;code = 98
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char = t;code = 116
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char = t;code = 116
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char = i;code = 105
char = n;code = 110
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char = W;code = 87
char = I;code = 73
char = 3;code = 51
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char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ,;code = 44
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char = s;code = 115
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char = g;code = 103
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = t;code = 116
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char = t;code = 116
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char = i;code = 105
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char = i;code = 105
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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 = y;code = 121
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char = e;code = 101
char = t;code = 116
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char = o;code = 111
char = f;code = 102
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char = M;code = 77
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char = -;code = 45
char = 4;code = 52
char = .;code = 46
char = ;code = 32
char = R;code = 82
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char = o;code = 111
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char = 0;code = 48
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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 = T;code = 84
char = a;code = 97
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char = f;code = 102
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char = w;code = 119
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char = a;code = 97
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char = k;code = 107
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char = i;code = 105
char = a;code = 97
char = l;code = 108
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char = g;code = 103
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result sql = Resveratrol (R-3), a trihydroxy trans-stilbene from grape, inhibits multistage carcinogenesis in animal models. A resveratrol derivative 3,4,5,4'-tetrahydroxystilbene (R-4) exhibits potent growth inhibitory effect against transformed human cells. Here we report that 3,4,5,4'-tetramethoxystilbene (MR-4), converted from R-4, was more potent against cancer cell lines (WI38VA, IMR-90SV, HeLa, LNCaP, HT-29, and HepG2), but had almost no inhibitory effect on the growth of normal cells (WI38, IMR-90, BJ-T) at the concentrations tested. The IC50 value of MR-4 on the growth inhibition of transformed WI38VA human cells was 0.5 microM, as compared to the value of greater than 50 microM for the normal WI38 cells. Resveratrol, however, did not exhibit such clear differential effect and the IC50 value of R-3 for WI38VA cells was about 50 microM. The growth inhibitory effect of MR-4 correlated with the induction of apoptosis in the transformed cells. When normal WI38 cells and transformed WI38VA cells were compared, MR-4 induced increases of the Bax/Bcl-2 mRNA ratio, p53 and Bax protein level, activation of caspases, and DNA fragmentation in transformed, but not in normal cells. Further analysis revealed that MR-4 caused a rapid appearance of perinuclear aggregation of mitochondria in WI38VA but not in WI38 cells, suggesting that the mitochondria could serve as an early target of MR-4. R-3 also induced apoptosis and mitochondrial clustering but only at a much higher concentration, close to 500 microM. Taken together, the specific activation of the mitochondria-mediated apoptotic pathway could be a major reason for the striking differential growth inhibitory effect of MR-4.
Publication: Br. J. Cancer 2005 Feb 14 ;92(3)::513-21.
Publication Date: 2005 Feb 14
Study Author(s): Gosslau, A;Chen, M;Ho, Ci-T;Chen, K Y;
Institution: Department of Chemistry and Chemical Biology, Center for Advanced Food Technology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8087, USA.
Shortcut link to this study:
Publication Date: 2005 Feb 14
Study Author(s): Gosslau, A;Chen, M;Ho, Ci-T;Chen, K Y;
Institution: Department of Chemistry and Chemical Biology, Center for Advanced Food Technology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8087, USA.
Shortcut link to this study:
Resveratrol (R-3), a trihydroxy trans-stilbene from grape, inhibits multistage carcinogenesis in animal models. A resveratrol derivative 3,4,5,4'-tetrahydroxystilbene (R-4) exhibits potent growth inhibitory effect against transformed human cells. Here we report that 3,4,5,4'-tetramethoxystilbene (MR-4), converted from R-4, was more potent against cancer cell lines (WI38VA, IMR-90SV, HeLa, LNCaP, HT-29, and HepG2), but had almost no inhibitory effect on the growth of normal cells (WI38, IMR-90, BJ-T) at the concentrations tested. The IC50 value of MR-4 on the growth inhibition of transformed WI38VA human cells was 0.5 microM, as compared to the value of greater than 50 microM for the normal WI38 cells. Resveratrol, however, did not exhibit such clear differential effect and the IC50 value of R-3 for WI38VA cells was about 50 microM. The growth inhibitory effect of MR-4 correlated with the induction of apoptosis in the transformed cells. When normal WI38 cells and transformed WI38VA cells were compared, MR-4 induced increases of the Bax/Bcl-2 mRNA ratio, p53 and Bax protein level, activation of caspases, and DNA fragmentation in transformed, but not in normal cells. Further analysis revealed that MR-4 caused a rapid appearance of perinuclear aggregation of mitochondria in WI38VA but not in WI38 cells, suggesting that the mitochondria could serve as an early target of MR-4. R-3 also induced apoptosis and mitochondrial clustering but only at a much higher concentration, close to 500 microM. Taken together, the specific activation of the mitochondria-mediated apoptotic pathway could be a major reason for the striking differential growth inhibitory effect of MR-4.
PMID: 15668717
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