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result sql = Quantitative combination effects between sulforaphane and 3,3'-diindolylmethane on proliferation of human colon cancer cells in vitro.
Quantitative combination effects between sulforaphane and 3,3'-diindolylmethane on proliferation of human colon cancer cells in vitro.
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char = <;code = 60
char = ;code = 32
char = 1;code = 49
char = ,;code = 44
char = ;code = 32
char = C;code = 67
char = I;code = 73
char = ;code = 32
char = =;code = 61
char = ;code = 32
char = 1;code = 49
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = C;code = 67
char = I;code = 73
char = ;code = 32
char = >;code = 62
char = ;code = 32
char = 1;code = 49
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = e;code = 101
char = r;code = 114
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char = i;code = 105
char = s;code = 115
char = m;code = 109
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char = ;code = 32
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
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char = o;code = 111
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = g;code = 103
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = ,;code = 44
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = n;code = 110
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char = a;code = 97
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = a;code = 97
char = l;code = 108
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char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
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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
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char = o;code = 111
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char = ;code = 32
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char = .;code = 46
char = 5;code = 53
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char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
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char = M;code = 77
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = b;code = 98
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = S;code = 83
char = F;code = 70
char = N;code = 78
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = D;code = 68
char = I;code = 73
char = M;code = 77
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = g;code = 103
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = .;code = 46
char = ;code = 32
char = W;code = 87
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char = t;code = 116
char = h;code = 104
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 = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
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 = s;code = 115
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = g;code = 103
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = u;code = 117
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = g;code = 103
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = b;code = 98
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
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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 = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 4;code = 52
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = M;code = 77
char = .;code = 46
char = ;code = 32
char = C;code = 67
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = -;code = 45
char = c;code = 99
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = e;code = 101
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char = a;code = 97
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = y;code = 121
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
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char = <;code = 60
char = b;code = 98
char = >;code = 62
char = <;code = 60
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char = r;code = 114
char = /;code = 47
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char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = S;code = 83
char = F;code = 70
char = N;code = 78
char = :;code = 58
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char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = ;code = 32
char = <;code = 60
char = /;code = 47
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char = >;code = 62
char = D;code = 68
char = I;code = 73
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char = r;code = 114
char = a;code = 97
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char = i;code = 105
char = o;code = 111
char = s;code = 115
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char = o;code = 111
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char = 1;code = 49
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char = 1;code = 49
char = ,;code = 44
char = ;code = 32
char = 1;code = 49
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char = 2;code = 50
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char = a;code = 97
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char = 1;code = 49
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char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = t;code = 116
char = o;code = 111
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char = a;code = 97
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char = c;code = 99
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char = n;code = 110
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char = n;code = 110
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char = a;code = 97
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char = i;code = 105
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char = s;code = 115
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char = b;code = 98
char = e;code = 101
char = t;code = 116
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = n;code = 110
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char = 1;code = 49
char = 0;code = 48
char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = 2;code = 50
char = 5;code = 53
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char = m;code = 109
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char = c;code = 99
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char = o;code = 111
char = M;code = 77
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = f;code = 102
char = i;code = 105
char = r;code = 114
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
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char = t;code = 116
char = a;code = 97
char = g;code = 103
char = o;code = 111
char = n;code = 110
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char = s;code = 115
char = m;code = 109
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = w;code = 119
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = i;code = 105
char = t;code = 116
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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
char = c;code = 99
char = t;code = 116
char = s;code = 115
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char = a;code = 97
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char = ;code = 32
char = h;code = 104
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = e;code = 101
char = r;code = 114
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char = d;code = 100
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = F;code = 70
char = N;code = 78
char = ;code = 32
char = (;code = 40
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
char = o;code = 111
char = M;code = 77
char = );code = 41
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = c;code = 99
char = o;code = 111
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char = b;code = 98
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = D;code = 68
char = I;code = 73
char = M;code = 77
char = ;code = 32
char = (;code = 40
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
char = o;code = 111
char = M;code = 77
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char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = s;code = 115
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = G;code = 71
char = (;code = 40
char = 2;code = 50
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char = /;code = 47
char = M;code = 77
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = -;code = 45
char = c;code = 99
char = y;code = 121
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char = l;code = 108
char = e;code = 101
char = ;code = 32
char = a;code = 97
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char = s;code = 115
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
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char = a;code = 97
char = s;code = 115
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char = n;code = 110
char = o;code = 111
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char = o;code = 111
char = b;code = 98
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char = e;code = 101
char = r;code = 114
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char = p;code = 112
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char = .;code = 46
char = ;code = 32
char = O;code = 79
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char = r;code = 114
char = e;code = 101
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char = a;code = 97
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char = i;code = 105
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char = c;code = 99
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char = a;code = 97
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char = i;code = 105
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char = s;code = 115
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char = o;code = 111
char = f;code = 102
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char = <;code = 60
char = b;code = 98
char = >;code = 62
char = <;code = 60
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char = r;code = 114
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char = <;code = 60
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char = <;code = 60
char = b;code = 98
char = >;code = 62
char = S;code = 83
char = F;code = 70
char = N;code = 78
char = :;code = 58
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char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = ;code = 32
char = <;code = 60
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char = b;code = 98
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char = D;code = 68
char = I;code = 73
char = M;code = 77
char = ;code = 32
char = c;code = 99
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char = b;code = 98
char = i;code = 105
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char = a;code = 97
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char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
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char = l;code = 108
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char = p;code = 112
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char = o;code = 111
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char = e;code = 101
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char = a;code = 97
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char = c;code = 99
char = a;code = 97
char = l;code = 108
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char = y;code = 121
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char = A;code = 65
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char = ;code = 32
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char = o;code = 111
char = w;code = 119
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char = a;code = 97
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char = n;code = 110
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char = t;code = 116
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char = a;code = 97
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char = i;code = 105
char = o;code = 111
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char = (;code = 40
char = b;code = 98
char = e;code = 101
char = l;code = 108
char = o;code = 111
char = w;code = 119
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char = 2;code = 50
char = 0;code = 48
char = ;code = 32
char = m;code = 109
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char = c;code = 99
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char = o;code = 111
char = M;code = 77
char = );code = 41
char = ,;code = 44
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char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
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char = ;code = 32
char = a;code = 97
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char = ;code = 32
char = p;code = 112
char = h;code = 104
char = y;code = 121
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = l;code = 108
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result sql = Isothiocyanates (ITCs) and indoles derived from cruciferous vegetables possess growth-inhibiting and apoptosis-inducing activities in cancer cell lines in vitro. ITCs like sulforaphane (SFN) are cytotoxic, whereas indoles including indole-3-carbinol or its condensation product 3,3'-diindolylmethane (DIM) are acting by cytostatic mechanisms in human colon cancer cell lines. In the present study, we have investigated the impact of defined combinations of SFN and DIM (ratio 1:4, 1:2, 1:1, 2:1 and 4:1) on cell proliferation, cell-cycle progression and apoptosis induction in cultured 40-16 colon carcinoma cells. Calculations of combination effects were based on the method of Chou et al. (1984) Adv. Enzyme Regul., 22, 27-55, and were expressed as a combination index (CI) with CI < 1, CI = 1 or CI > 1 representing synergism, additivity or antagonism, respectively. Interestingly, at a total drug concentration of 2.5 microM, all combinations of SFN and DIM were antagonistic. With increasing concentrations, the antagonistic effect gradually turned into a synergistic interaction at the highest combined cytotoxic concentration of 40 microM. Cell-cycle analyses with

SFN:
DIM ratios of 1:1, 1:2 and 1:4 and total concentrations between 10 and 25 microM confirmed antagonism at low and additive effects at higher doses. SFN (10 microM) in combination with DIM (10 microM) resulted in strong G(2)/M cell-cycle arrest, which was not observed with either compound alone. Our results indicate that cytotoxic concentrations of

SFN:
DIM combinations affect cell proliferation synergistically. At low total concentrations (below 20 microM), which are physiologically more relevant, the combined broccoli compounds showed antagonistic interactions in terms of cell growth inhibition. These data stress the need for elucidating mechanistic interactions for better predicting beneficial health effects of bioactive food components.

Publication: Carcinogenesis 2007 Jul ;28(7)::1471-7.
Publication Date: 2007 Jul
Study Author(s): Pappa, Gerlinde;Strathmann, Julia;Löwinger, Maria;Bartsch, Helmut;Gerhäuser, Clarissa;
Institution: Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), C010-2 Chemoprevention, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Shortcut link to this study:
Isothiocyanates (ITCs) and indoles derived from cruciferous vegetables possess growth-inhibiting and apoptosis-inducing activities in cancer cell lines in vitro. ITCs like sulforaphane (SFN) are cytotoxic, whereas indoles including indole-3-carbinol or its condensation product 3,3'-diindolylmethane (DIM) are acting by cytostatic mechanisms in human colon cancer cell lines. In the present study, we have investigated the impact of defined combinations of SFN and DIM (ratio 1:4, 1:2, 1:1, 2:1 and 4:1) on cell proliferation, cell-cycle progression and apoptosis induction in cultured 40-16 colon carcinoma cells. Calculations of combination effects were based on the method of Chou et al. (1984) Adv. Enzyme Regul., 22, 27-55, and were expressed as a combination index (CI) with CI < 1, CI = 1 or CI > 1 representing synergism, additivity or antagonism, respectively. Interestingly, at a total drug concentration of 2.5 microM, all combinations of SFN and DIM were antagonistic. With increasing concentrations, the antagonistic effect gradually turned into a synergistic interaction at the highest combined cytotoxic concentration of 40 microM. Cell-cycle analyses with

SFN:
DIM ratios of 1:1, 1:2 and 1:4 and total concentrations between 10 and 25 microM confirmed antagonism at low and additive effects at higher doses. SFN (10 microM) in combination with DIM (10 microM) resulted in strong G(2)/M cell-cycle arrest, which was not observed with either compound alone. Our results indicate that cytotoxic concentrations of

SFN:
DIM combinations affect cell proliferation synergistically. At low total concentrations (below 20 microM), which are physiologically more relevant, the combined broccoli compounds showed antagonistic interactions in terms of cell growth inhibition. These data stress the need for elucidating mechanistic interactions for better predicting beneficial health effects of bioactive food components.
PMID: 17331956

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