|
|
char = R;code = 82
char = e;code = 101
char = s;code = 115
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = -;code = 45
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char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
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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 = M;code = 77
char = C;code = 67
char = F;code = 70
char = -;code = 45
char = 7;code = 55
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 = 32
char = i;code = 105
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char = o;code = 111
char = l;code = 108
char = v;code = 118
char = e;code = 101
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char = ;code = 32
char = a;code = 97
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 = m;code = 109
char = e;code = 101
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = m;code = 109
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char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = w;code = 119
char = n;code = 110
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 = B;code = 66
char = c;code = 99
char = l;code = 108
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = N;code = 78
char = F;code = 70
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char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
char = B;code = 66
char = .;code = 46
result sql = Resveratrol-induced apoptosis in MCF-7 human breast cancer cells involves a caspase-independent mechanism with downregulation of Bcl-2 and NF-kappaB.
Resveratrol-induced apoptosis in MCF-7 human breast cancer cells involves a caspase-independent mechanism with downregulation of Bcl-2 and NF-kappaB.char = R;code = 82
char = e;code = 101
char = s;code = 115
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = (;code = 40
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = m;code = 109
char = o;code = 111
char = p;code = 112
char = r;code = 114
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char = v;code = 118
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
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char = m;code = 109
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char = u;code = 117
char = l;code = 108
char = e;code = 101
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char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
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char = t;code = 116
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = f;code = 102
char = e;code = 101
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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
char = f;code = 102
char = ;code = 32
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char = u;code = 117
char = m;code = 109
char = o;code = 111
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 = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = i;code = 105
char = e;code = 101
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char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = i;code = 105
char = o;code = 111
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char = l;code = 108
char = y;code = 121
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = u;code = 117
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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 = i;code = 105
char = s;code = 115
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 = b;code = 98
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char = e;code = 101
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = u;code = 117
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
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char = ;code = 32
char = b;code = 98
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char = ;code = 32
char = i;code = 105
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char = e;code = 101
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char = f;code = 102
char = e;code = 101
char = r;code = 114
char = i;code = 105
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char = w;code = 119
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char = t;code = 116
char = h;code = 104
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char = E;code = 69
char = R;code = 82
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char = a;code = 97
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char = d;code = 100
char = e;code = 101
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char = p;code = 112
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char = p;code = 112
char = h;code = 104
char = o;code = 111
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char = n;code = 110
char = o;code = 111
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char = i;code = 105
char = t;code = 116
char = i;code = 105
char = d;code = 100
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char = e;code = 101
char = ;code = 32
char = (;code = 40
char = P;code = 80
char = I;code = 73
char = 3;code = 51
char = K;code = 75
char = );code = 41
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = w;code = 119
char = a;code = 97
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = y;code = 121
char = z;code = 122
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 = a;code = 97
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = m;code = 109
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = P;code = 80
char = I;code = 73
char = 3;code = 51
char = K;code = 75
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = -;code = 45
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 = d;code = 100
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 = 46
char = ;code = 32
char = A;code = 65
char = p;code = 112
char = o;code = 111
char = p;code = 112
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char = o;code = 111
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = h;code = 104
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char = b;code = 98
char = y;code = 121
char = ;code = 32
char = R;code = 82
char = E;code = 69
char = S;code = 83
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 = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = B;code = 66
char = c;code = 99
char = l;code = 108
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char = 2;code = 50
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char = i;code = 105
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char = x;code = 120
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char = s;code = 115
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char = a;code = 97
char = b;code = 98
char = o;code = 111
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char = a;code = 97
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char = e;code = 101
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char = e;code = 101
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char = c;code = 99
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char = S;code = 83
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result sql = Resveratrol (RES), a chemopreventive molecule, inhibits the proliferation of tumor cells of different etiologies. We previously showed that RES alters the cell cycle and induces apoptosis in MCF-7 breast tumor cells by interfering with the estrogen receptor (ERaalpha)-dependent phosphoinositide 3-kinase (PI3K) pathway. Here, we analyzed signaling downstream of PI3K, to understand the mechanisms of RES-induced apoptosis. Apoptotic death by RES in MCF-7 was mediated by Bcl-2 downregulation since overexpression of this protein abolished apoptosis. Decreased Bcl-2 levels were not related to cytochrome c release, activation of caspases 3/8 or poly(ADP-ribose) polymerase proteolysis. However, RES decreased mitochondrial membrane potential and increased reactive oxygen species and nitric oxide production. NF-kappaB, a regulator of Bcl-2 expression, and calpain protease activity, a regulator of NF-kappaB, were both inhibited by RES. The patterns for NF-kappaB and calpain activities followed that of PI3K and were inhibited by LY294002. NF-kappaB inhibition coincided with diminished MMP-9 activity and cell migration. These data suggest that RES-induced apoptosis in MCF-7 could involve an oxidative, caspase-independent mechanism, whereby inhibition of PI3K signaling converges to Bcl-2 through NF-kappaB and calpain protease activity. Therefore, Bcl-2 and NF-kappaB could be considered potential targets for the chemopreventive activity of RES in estrogen-responsive tumor cells.
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result sql = Resveratrol-induced apoptosis in MCF-7 human breast cancer cells involves a caspase-independent mechanism with downregulation of Bcl-2 and NF-kappaB.
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char = a;code = 97
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = (;code = 40
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = m;code = 109
char = o;code = 111
char = p;code = 112
char = r;code = 114
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char = v;code = 118
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
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char = m;code = 109
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = e;code = 101
char = ,;code = 44
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
char = s;code = 115
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char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = u;code = 117
char = m;code = 109
char = o;code = 111
char = r;code = 114
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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 = o;code = 111
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char = ;code = 32
char = d;code = 100
char = i;code = 105
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
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char = p;code = 112
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = i;code = 105
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = s;code = 115
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char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = e;code = 101
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 = 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 = 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 = M;code = 77
char = C;code = 67
char = F;code = 70
char = -;code = 45
char = 7;code = 55
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 = t;code = 116
char = u;code = 117
char = m;code = 109
char = o;code = 111
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 = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
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 = 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 = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = (;code = 40
char = E;code = 69
char = R;code = 82
char = a;code = 97
char = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
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char = e;code = 101
char = p;code = 112
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char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = 3;code = 51
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char = k;code = 107
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = (;code = 40
char = P;code = 80
char = I;code = 73
char = 3;code = 51
char = K;code = 75
char = );code = 41
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = w;code = 119
char = a;code = 97
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ,;code = 44
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char = w;code = 119
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = y;code = 121
char = z;code = 122
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 = a;code = 97
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = m;code = 109
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = P;code = 80
char = I;code = 73
char = 3;code = 51
char = K;code = 75
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = t;code = 116
char = a;code = 97
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = m;code = 109
char = e;code = 101
char = c;code = 99
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char = a;code = 97
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char = i;code = 105
char = s;code = 115
char = m;code = 109
char = s;code = 115
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = -;code = 45
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
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char = a;code = 97
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char = o;code = 111
char = p;code = 112
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char = o;code = 111
char = s;code = 115
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char = s;code = 115
char = .;code = 46
char = ;code = 32
char = A;code = 65
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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 = c;code = 99
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char = t;code = 116
char = h;code = 104
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char = b;code = 98
char = y;code = 121
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char = R;code = 82
char = E;code = 69
char = S;code = 83
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = M;code = 77
char = C;code = 67
char = F;code = 70
char = -;code = 45
char = 7;code = 55
char = ;code = 32
char = w;code = 119
char = a;code = 97
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char = a;code = 97
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char = b;code = 98
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char = ;code = 32
char = B;code = 66
char = c;code = 99
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char = -;code = 45
char = 2;code = 50
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char = w;code = 119
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char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
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char = i;code = 105
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char = ;code = 32
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char = c;code = 99
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char = e;code = 101
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char = s;code = 115
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char = o;code = 111
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char = o;code = 111
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char = ;code = 32
char = t;code = 116
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char = i;code = 105
char = s;code = 115
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char = p;code = 112
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char = a;code = 97
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char = a;code = 97
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char = o;code = 111
char = p;code = 112
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char = o;code = 111
char = s;code = 115
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char = s;code = 115
char = .;code = 46
char = ;code = 32
char = D;code = 68
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char = c;code = 99
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char = a;code = 97
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char = B;code = 66
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char = e;code = 101
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char = e;code = 101
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char = e;code = 101
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char = c;code = 99
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char = h;code = 104
char = r;code = 114
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char = m;code = 109
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char = e;code = 101
char = a;code = 97
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char = e;code = 101
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char = ;code = 32
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char = i;code = 105
char = v;code = 118
char = a;code = 97
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char = o;code = 111
char = f;code = 102
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char = p;code = 112
char = a;code = 97
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char = e;code = 101
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char = 3;code = 51
char = /;code = 47
char = 8;code = 56
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char = o;code = 111
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char = o;code = 111
char = l;code = 108
char = y;code = 121
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char = D;code = 68
char = P;code = 80
char = -;code = 45
char = r;code = 114
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char = b;code = 98
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char = e;code = 101
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char = e;code = 101
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char = o;code = 111
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char = .;code = 46
char = ;code = 32
char = H;code = 72
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char = e;code = 101
char = v;code = 118
char = e;code = 101
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char = ;code = 32
char = R;code = 82
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char = S;code = 83
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char = a;code = 97
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char = v;code = 118
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char = u;code = 117
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char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = .;code = 46
char = ;code = 32
char = N;code = 78
char = F;code = 70
char = -;code = 45
char = k;code = 107
char = a;code = 97
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char = p;code = 112
char = a;code = 97
char = B;code = 66
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char = r;code = 114
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char = f;code = 102
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char = i;code = 105
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char = ,;code = 44
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char = a;code = 97
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char = p;code = 112
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char = t;code = 116
char = e;code = 101
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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 = a;code = 97
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char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = N;code = 78
char = F;code = 70
char = -;code = 45
char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
char = B;code = 66
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
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char = b;code = 98
char = o;code = 111
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char = h;code = 104
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char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
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result sql = Resveratrol (RES), a chemopreventive molecule, inhibits the proliferation of tumor cells of different etiologies. We previously showed that RES alters the cell cycle and induces apoptosis in MCF-7 breast tumor cells by interfering with the estrogen receptor (ERaalpha)-dependent phosphoinositide 3-kinase (PI3K) pathway. Here, we analyzed signaling downstream of PI3K, to understand the mechanisms of RES-induced apoptosis. Apoptotic death by RES in MCF-7 was mediated by Bcl-2 downregulation since overexpression of this protein abolished apoptosis. Decreased Bcl-2 levels were not related to cytochrome c release, activation of caspases 3/8 or poly(ADP-ribose) polymerase proteolysis. However, RES decreased mitochondrial membrane potential and increased reactive oxygen species and nitric oxide production. NF-kappaB, a regulator of Bcl-2 expression, and calpain protease activity, a regulator of NF-kappaB, were both inhibited by RES. The patterns for NF-kappaB and calpain activities followed that of PI3K and were inhibited by LY294002. NF-kappaB inhibition coincided with diminished MMP-9 activity and cell migration. These data suggest that RES-induced apoptosis in MCF-7 could involve an oxidative, caspase-independent mechanism, whereby inhibition of PI3K signaling converges to Bcl-2 through NF-kappaB and calpain protease activity. Therefore, Bcl-2 and NF-kappaB could be considered potential targets for the chemopreventive activity of RES in estrogen-responsive tumor cells.
Publication: Int. J. Cancer 2005 May 20 ;115(1)::74-84.
Publication Date: 2005 May 20
Study Author(s): Pozo-Guisado, Eulalia;Merino, Jaime M;Mulero-Navarro, Sonia;Lorenzo-Benayas, M Jesús;Centeno, Francisco;Alvarez-Barrientos, Alberto;Fernandez-Salguero, Pedro M;Salguero, Pedro M Fernandez;
Institution: Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Ciencias, Universidad de Extremadura, Badajoz, Spain.
Shortcut link to this study:
Publication Date: 2005 May 20
Study Author(s): Pozo-Guisado, Eulalia;Merino, Jaime M;Mulero-Navarro, Sonia;Lorenzo-Benayas, M Jesús;Centeno, Francisco;Alvarez-Barrientos, Alberto;Fernandez-Salguero, Pedro M;Salguero, Pedro M Fernandez;
Institution: Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Ciencias, Universidad de Extremadura, Badajoz, Spain.
Shortcut link to this study:
Resveratrol (RES), a chemopreventive molecule, inhibits the proliferation of tumor cells of different etiologies. We previously showed that RES alters the cell cycle and induces apoptosis in MCF-7 breast tumor cells by interfering with the estrogen receptor (ERaalpha)-dependent phosphoinositide 3-kinase (PI3K) pathway. Here, we analyzed signaling downstream of PI3K, to understand the mechanisms of RES-induced apoptosis. Apoptotic death by RES in MCF-7 was mediated by Bcl-2 downregulation since overexpression of this protein abolished apoptosis. Decreased Bcl-2 levels were not related to cytochrome c release, activation of caspases 3/8 or poly(ADP-ribose) polymerase proteolysis. However, RES decreased mitochondrial membrane potential and increased reactive oxygen species and nitric oxide production. NF-kappaB, a regulator of Bcl-2 expression, and calpain protease activity, a regulator of NF-kappaB, were both inhibited by RES. The patterns for NF-kappaB and calpain activities followed that of PI3K and were inhibited by LY294002. NF-kappaB inhibition coincided with diminished MMP-9 activity and cell migration. These data suggest that RES-induced apoptosis in MCF-7 could involve an oxidative, caspase-independent mechanism, whereby inhibition of PI3K signaling converges to Bcl-2 through NF-kappaB and calpain protease activity. Therefore, Bcl-2 and NF-kappaB could be considered potential targets for the chemopreventive activity of RES in estrogen-responsive tumor cells.
PMID: 15688415
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