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result sql = Evidence for a biphasic apoptotic pathway induced by melatonin in MCF-7 breast cancer cells.

Evidence for a biphasic apoptotic pathway induced by melatonin in MCF-7 breast cancer cells.

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char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = u;code = 117
char = p;code = 112
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = 1;code = 49
char = 4;code = 52
char = 4;code = 52
char = ;code = 32
char = h;code = 104
char = r;code = 114
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = ,;code = 44
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 = 45
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 = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = s;code = 115
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 = i;code = 105
char = n;code = 110
char = g;code = 103
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 = f;code = 102
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = ;code = 32
char = 1;code = 49
char = ;code = 32
char = (;code = 40
char = T;code = 84
char = G;code = 71
char = F;code = 70
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = 1;code = 49
char = );code = 41
char = -;code = 45
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 = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = t;code = 116
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = -;code = 45
char = T;code = 84
char = G;code = 71
char = F;code = 70
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = 1;code = 49
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = b;code = 98
char = o;code = 111
char = d;code = 100
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = M;code = 77
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
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 = ;code = 32
char = r;code = 114
char = i;code = 105
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
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 = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = 2;code = 50
char = 4;code = 52
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 9;code = 57
char = 6;code = 54
char = ;code = 32
char = h;code = 104
char = r;code = 114
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = -;code = 45
char = T;code = 84
char = G;code = 71
char = F;code = 70
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = 1;code = 49
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = b;code = 98
char = o;code = 111
char = d;code = 100
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = m;code = 109
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = l;code = 108
char = y;code = 121
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 = e;code = 101
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = n;code = 110
char = -;code = 45
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 = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
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 = 59
char = ;code = 32
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = l;code = 108
char = y;code = 121
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 = s;code = 115
char = ;code = 32
char = u;code = 117
char = n;code = 110
char = a;code = 97
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = E;code = 69
char = a;code = 97
char = r;code = 114
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = r;code = 114
char = a;code = 97
char = m;code = 109
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 = ;code = 32
char = d;code = 100
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = o;code = 111
char = c;code = 99
char = i;code = 105
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 = a;code = 97
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 = ;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
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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 = p;code = 112
char = 5;code = 53
char = 3;code = 51
char = /;code = 47
char = M;code = 77
char = D;code = 68
char = M;code = 77
char = 2;code = 50
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 = 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 = A;code = 65
char = I;code = 73
char = F;code = 70
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
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 = i;code = 105
char = n;code = 110
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 = ;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 = y;code = 121
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = -;code = 45
char = P;code = 80
char = A;code = 65
char = R;code = 82
char = P;code = 80
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = A;code = 65
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 = e;code = 101
char = d;code = 100
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 = 45
char = 9;code = 57
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = -;code = 45
char = 7;code = 55
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = -;code = 45
char = P;code = 80
char = A;code = 65
char = R;code = 82
char = P;code = 80
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 = 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 = a;code = 97
char = t;code = 116
char = ;code = 32
char = 9;code = 57
char = 6;code = 54
char = ;code = 32
char = h;code = 104
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 = o;code = 111
char = m;code = 109
char = i;code = 105
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = -;code = 45
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
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 = ;code = 32
char = B;code = 66
char = c;code = 99
char = l;code = 108
char = -;code = 45
char = 2;code = 50
char = /;code = 47
char = B;code = 66
char = a;code = 97
char = x;code = 120
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 = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
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char = d;code = 100
char = a;code = 97
char = t;code = 116
char = a;code = 97
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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 = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = w;code = 119
char = o;code = 111
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char = d;code = 100
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = t;code = 116
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 = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = g;code = 103
char = g;code = 103
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = M;code = 77
char = C;code = 67
char = F;code = 70
char = -;code = 45
char = 7;code = 55
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 = 58
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = l;code = 108
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = T;code = 84
char = G;code = 71
char = F;code = 70
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = 1;code = 49
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 = s;code = 115
char = p;code = 112
char = a;code = 97
char = s;code = 115
char = e;code = 101
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 = 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 = e;code = 101
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
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 = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = T;code = 84
char = G;code = 71
char = F;code = 70
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = 1;code = 49
char = -;code = 45
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 = p;code = 112
char = r;code = 114
char = o;code = 111
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = 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 = e;code = 101
char = d;code = 100
char = -;code = 45
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 = -;code = 45
char = 7;code = 55
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = k;code = 107
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = l;code = 108
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 = o;code = 111
char = r;code = 114
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
result sql = Previous investigations demonstrated that melatonin exerts an oncostatic action on estrogen-responsive breast cancer, both in vitro and in vivo. Nevertheless, the pro-apoptotic effect of melatonin is still a matter of debate. An experimental study was undertaken to focus on melatonin-related apoptosis and to identify the apoptotic pathways involved. Whole cell-count, flow-cytometry analysis and proteins involved in apoptotic pathways [p53, p73, murine double minute 2 (MDM2), caspases-9,-7,-6, cleaved-poly ADP ribose polymerase (PARP), Bcl-2, Bax and apoptotic inducing factor (AIF)] were investigated in human MCF-7 breast cancer cells treated with physiological (1 nM) concentration of melatonin. Melatonin exerts a significant growth-inhibitory effect on MCF-7 cells, becoming evident after 72 hr and thereafter increasing linearly up to 144 hr. In this model, the growth-inhibition is transforming growth factor beta 1 (TGFbeta1)-dependent and it might be reversed by adding an anti-TGFbeta1 antibody. Melatonin induces a significant rise in apoptotic rate, at both 24 and 96 hr. The anti-TGFbeta1 antibody almost completely suppresses melatonin-related late apoptosis; however, early apoptosis is unaffected. Early programmed cell death is associated with a significant increase in the p53/MDM2 ratio and in AIF release, without modifications in caspase activity or cleaved-PARP levels. Activated caspases-9 and -7 and cleaved-PARP increased significantly at 96 hr, concomitantly with a down-regulation of the Bcl-2/Bax ratio. These data suggest that two distinct apoptotic processes are triggered by melatonin in MCF-7 cells: an early, TGFbeta1 and caspase-independent response, and a late apoptotic TGFbeta1-dependent process in which activated-caspase-7 is likely to be the terminal effector.

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