|
|
char = 1;code = 49
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char = l;code = 108
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result sql = 1-Benzyl-indole-3-carbinol is a novel indole-3-carbinol derivative with significantly enhanced potency of anti-proliferative and anti-estrogenic properties in human breast cancer cells.
1-Benzyl-indole-3-carbinol is a novel indole-3-carbinol derivative with significantly enhanced potency of anti-proliferative and anti-estrogenic properties in human breast cancer cells.char = I;code = 73
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char = -;code = 45
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char = b;code = 98
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char = ;code = 32
char = (;code = 40
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char = ;code = 32
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char = g;code = 103
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char = a;code = 97
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char = a;code = 97
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result sql = Indole-3-carbinol (I3C), a natural autolysis product of a gluccosinolate present in Brassica vegetables such as broccoli and cabbage, has anti-proliferative and anti-estrogenic activities in human breast cancer cells. A new and significantly more potent I3C analogue, 1-benzyl-I3C was synthesized, and in comparison to I3C, this novel derivative displayed an approximate 1000-fold enhanced potency in suppressing the growth of both estrogen responsive (MCF-7) and estrogen-independent (MDA-MB-231) human breast cancer cells (I3C IC(50) of 52 microM, and 1-benzyl-I3C IC(50) of 0.05 microM). At significantly lower concentrations, 1-benzyl-I3C induced a robust G1 cell cycle arrest and elicited the key I3C-specific effects on expression and activity of G1-acting cell cycle genes including the disruption of endogenous interactions of the Sp1 transcription factor with the CDK6 promoter. Furthermore, in estrogen responsive MCF-7 cells, with enhanced potency 1-benzyl-I3C down-regulated production of estrogen receptor-alpha protein, acts with tamoxifen to arrest breast cancer cell growth more effectively than either compound alone, and inhibited the in vivo growth of human breast cancer cell-derived tumor xenografts in athymic mice. Our results implicate 1-benzyl-I3C as a novel, potent inhibitor of human breast cancer proliferation and estrogen responsiveness that could potentially be developed into a promising therapeutic agent for the treatment of indole-sensitive cancers.
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char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = -;code = 45
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = h;code = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = t;code = 116
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 = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = .;code = 46
result sql = 1-Benzyl-indole-3-carbinol is a novel indole-3-carbinol derivative with significantly enhanced potency of anti-proliferative and anti-estrogenic properties in human breast cancer cells.
char = n;code = 110
char = d;code = 100
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = -;code = 45
char = 3;code = 51
char = -;code = 45
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = b;code = 98
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = (;code = 40
char = I;code = 73
char = 3;code = 51
char = C;code = 67
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = n;code = 110
char = a;code = 97
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = u;code = 117
char = t;code = 116
char = o;code = 111
char = l;code = 108
char = y;code = 121
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = g;code = 103
char = l;code = 108
char = u;code = 117
char = c;code = 99
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
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 = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = B;code = 66
char = r;code = 114
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = ;code = 32
char = v;code = 118
char = e;code = 101
char = g;code = 103
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = r;code = 114
char = o;code = 111
char = c;code = 99
char = c;code = 99
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = b;code = 98
char = b;code = 98
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = -;code = 45
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 = v;code = 118
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = -;code = 45
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = h;code = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = t;code = 116
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 = 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 = A;code = 65
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = w;code = 119
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
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
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = I;code = 73
char = 3;code = 51
char = C;code = 67
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = u;code = 117
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = 1;code = 49
char = -;code = 45
char = b;code = 98
char = e;code = 101
char = n;code = 110
char = z;code = 122
char = y;code = 121
char = l;code = 108
char = -;code = 45
char = I;code = 73
char = 3;code = 51
char = C;code = 67
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = z;code = 122
char = e;code = 101
char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
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 = i;code = 105
char = s;code = 115
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = I;code = 73
char = 3;code = 51
char = C;code = 67
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = y;code = 121
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = 1;code = 49
char = 0;code = 48
char = 0;code = 48
char = 0;code = 48
char = -;code = 45
char = f;code = 102
char = o;code = 111
char = l;code = 108
char = d;code = 100
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = y;code = 121
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = p;code = 112
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
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 = o;code = 111
char = f;code = 102
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = M;code = 77
char = C;code = 67
char = F;code = 70
char = -;code = 45
char = 7;code = 55
char = );code = 41
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = -;code = 45
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = (;code = 40
char = M;code = 77
char = D;code = 68
char = A;code = 65
char = -;code = 45
char = M;code = 77
char = B;code = 66
char = -;code = 45
char = 2;code = 50
char = 3;code = 51
char = 1;code = 49
char = );code = 41
char = ;code = 32
char = h;code = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
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char = b;code = 98
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char = e;code = 101
char = a;code = 97
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char = c;code = 99
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char = c;code = 99
char = e;code = 101
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = I;code = 73
char = 3;code = 51
char = C;code = 67
char = ;code = 32
char = I;code = 73
char = C;code = 67
char = (;code = 40
char = 5;code = 53
char = 0;code = 48
char = );code = 41
char = ;code = 32
char = o;code = 111
char = f;code = 102
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char = 5;code = 53
char = 2;code = 50
char = ;code = 32
char = m;code = 109
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char = M;code = 77
char = ,;code = 44
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char = a;code = 97
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char = 1;code = 49
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char = b;code = 98
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char = z;code = 122
char = y;code = 121
char = l;code = 108
char = -;code = 45
char = I;code = 73
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char = C;code = 67
char = ;code = 32
char = I;code = 73
char = C;code = 67
char = (;code = 40
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char = o;code = 111
char = f;code = 102
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char = 0;code = 48
char = .;code = 46
char = 0;code = 48
char = 5;code = 53
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 = 46
char = ;code = 32
char = A;code = 65
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
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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 = t;code = 116
char = l;code = 108
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char = l;code = 108
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char = c;code = 99
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char = n;code = 110
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char = t;code = 116
char = r;code = 114
char = a;code = 97
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char = i;code = 105
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char = u;code = 117
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char = e;code = 101
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char = b;code = 98
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char = s;code = 115
char = t;code = 116
char = ;code = 32
char = G;code = 71
char = 1;code = 49
char = ;code = 32
char = c;code = 99
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char = l;code = 108
char = l;code = 108
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char = c;code = 99
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char = a;code = 97
char = r;code = 114
char = r;code = 114
char = e;code = 101
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char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
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char = c;code = 99
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char = e;code = 101
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char = k;code = 107
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char = y;code = 121
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char = I;code = 73
char = 3;code = 51
char = C;code = 67
char = -;code = 45
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = i;code = 105
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char = i;code = 105
char = c;code = 99
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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 = a;code = 97
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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 = f;code = 102
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char = 1;code = 49
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char = n;code = 110
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char = c;code = 99
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char = l;code = 108
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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 = g;code = 103
char = e;code = 101
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char = ;code = 32
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char = f;code = 102
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = S;code = 83
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char = 1;code = 49
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char = t;code = 116
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char = a;code = 97
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char = s;code = 115
char = c;code = 99
char = r;code = 114
char = i;code = 105
char = p;code = 112
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result sql = Indole-3-carbinol (I3C), a natural autolysis product of a gluccosinolate present in Brassica vegetables such as broccoli and cabbage, has anti-proliferative and anti-estrogenic activities in human breast cancer cells. A new and significantly more potent I3C analogue, 1-benzyl-I3C was synthesized, and in comparison to I3C, this novel derivative displayed an approximate 1000-fold enhanced potency in suppressing the growth of both estrogen responsive (MCF-7) and estrogen-independent (MDA-MB-231) human breast cancer cells (I3C IC(50) of 52 microM, and 1-benzyl-I3C IC(50) of 0.05 microM). At significantly lower concentrations, 1-benzyl-I3C induced a robust G1 cell cycle arrest and elicited the key I3C-specific effects on expression and activity of G1-acting cell cycle genes including the disruption of endogenous interactions of the Sp1 transcription factor with the CDK6 promoter. Furthermore, in estrogen responsive MCF-7 cells, with enhanced potency 1-benzyl-I3C down-regulated production of estrogen receptor-alpha protein, acts with tamoxifen to arrest breast cancer cell growth more effectively than either compound alone, and inhibited the in vivo growth of human breast cancer cell-derived tumor xenografts in athymic mice. Our results implicate 1-benzyl-I3C as a novel, potent inhibitor of human breast cancer proliferation and estrogen responsiveness that could potentially be developed into a promising therapeutic agent for the treatment of indole-sensitive cancers.
Publication: Chem. Biol. Interact. 2010 Aug 5 ;186(3)::255-66. :doi: 10.1016/j.cbi.2010.05.015.
Publication Date: 2010 Aug 5
Study Author(s): Nguyen, Hanh H;Lavrenov, Sergey N;Sundar, Shyam N;Nguyen, David H H;Tseng, Min;Marconett, Crystal N;Kung, Jenny;Staub, Richard E;Preobrazhenskaya, Maria N;Bjeldanes, Leonard F;Firestone, Gary L;
Institution: Department of Molecular and Cell Biology and The Cancer Research Laboratory, Univ. of California at Berkeley, Berkeley, CA 94720-3200, United States.
Shortcut link to this study:
Publication Date: 2010 Aug 5
Study Author(s): Nguyen, Hanh H;Lavrenov, Sergey N;Sundar, Shyam N;Nguyen, David H H;Tseng, Min;Marconett, Crystal N;Kung, Jenny;Staub, Richard E;Preobrazhenskaya, Maria N;Bjeldanes, Leonard F;Firestone, Gary L;
Institution: Department of Molecular and Cell Biology and The Cancer Research Laboratory, Univ. of California at Berkeley, Berkeley, CA 94720-3200, United States.
Shortcut link to this study:
Indole-3-carbinol (I3C), a natural autolysis product of a gluccosinolate present in Brassica vegetables such as broccoli and cabbage, has anti-proliferative and anti-estrogenic activities in human breast cancer cells. A new and significantly more potent I3C analogue, 1-benzyl-I3C was synthesized, and in comparison to I3C, this novel derivative displayed an approximate 1000-fold enhanced potency in suppressing the growth of both estrogen responsive (MCF-7) and estrogen-independent (MDA-MB-231) human breast cancer cells (I3C IC(50) of 52 microM, and 1-benzyl-I3C IC(50) of 0.05 microM). At significantly lower concentrations, 1-benzyl-I3C induced a robust G1 cell cycle arrest and elicited the key I3C-specific effects on expression and activity of G1-acting cell cycle genes including the disruption of endogenous interactions of the Sp1 transcription factor with the CDK6 promoter. Furthermore, in estrogen responsive MCF-7 cells, with enhanced potency 1-benzyl-I3C down-regulated production of estrogen receptor-alpha protein, acts with tamoxifen to arrest breast cancer cell growth more effectively than either compound alone, and inhibited the in vivo growth of human breast cancer cell-derived tumor xenografts in athymic mice. Our results implicate 1-benzyl-I3C as a novel, potent inhibitor of human breast cancer proliferation and estrogen responsiveness that could potentially be developed into a promising therapeutic agent for the treatment of indole-sensitive cancers.
PMID: 20570586
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