char = A;code = 65
char = p;code = 112
char = i;code = 105
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = n;code = 110
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 = p;code = 112
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = e;code = 101
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 = ;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 = i;code = 105
char = n;code = 110
char = i;code = 105
char = t;code = 116
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 = r;code = 114
char = e;code = 101
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = x;code = 120
char = y;code = 121
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = 5;code = 53
char = 3;code = 51
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
result sql = Apigenin-induced prostate cancer cell death is initiated by reactive oxygen species and p53 activation.
Apigenin-induced prostate cancer cell death is initiated by reactive oxygen species and p53 activation.
char = A;code = 65
char = p;code = 112
char = i;code = 105
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = f;code = 102
char = l;code = 108
char = a;code = 97
char = v;code = 118
char = o;code = 111
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char = e;code = 101
char = ,;code = 44
char = ;code = 32
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char = o;code = 111
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char = e;code = 101
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char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
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char = a;code = 97
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char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = l;code = 108
char = d;code = 100
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char = t;code = 116
char = y;code = 121
char = p;code = 112
char = e;code = 101
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char = p;code = 112
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char = 3;code = 51
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
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char = o;code = 111
char = p;code = 112
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char = c;code = 99
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
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char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
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char = u;code = 117
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char = d;code = 100
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char = d;code = 100
char = e;code = 101
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char = a;code = 97
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char = l;code = 108
char = e;code = 101
char = d;code = 100
char = ;code = 32
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char = t;code = 116
char = u;code = 117
char = d;code = 100
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char = e;code = 101
char = s;code = 115
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
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char = s;code = 115
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = s;code = 115
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 = o;code = 111
char = f;code = 102
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
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char = .;code = 46
char = ;code = 32
char = E;code = 69
char = x;code = 120
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char = ;code = 32
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char = p;code = 112
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char = o;code = 111
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char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
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char = 2;code = 50
char = 2;code = 50
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char = ;code = 32
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char = l;code = 108
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char = ;code = 32
char = h;code = 104
char = a;code = 97
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char = b;code = 98
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char = r;code = 114
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char = g;code = 103
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = l;code = 108
char = d;code = 100
char = -;code = 45
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char = e;code = 101
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char = p;code = 112
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char = 3;code = 51
char = ,;code = 44
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char = g;code = 103
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char = t;code = 116
char = h;code = 104
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char = p;code = 112
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char = s;code = 115
char = s;code = 115
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char = v;code = 118
char = e;code = 101
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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 = s;code = 115
char = ;code = 32
char = (;code = 40
char = 1;code = 49
char = 0;code = 48
char = -;code = 45
char = 8;code = 56
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 = o;code = 111
char = f;code = 102
char = ;code = 32
char = a;code = 97
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char = i;code = 105
char = g;code = 103
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = r;code = 114
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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
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = b;code = 98
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char = l;code = 108
char = i;code = 105
char = z;code = 122
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 = p;code = 112
char = 5;code = 53
char = 3;code = 51
char = ;code = 32
char = b;code = 98
char = y;code = 121
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
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char = y;code = 121
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = o;code = 111
char = n;code = 110
char = ;code = 32
char = c;code = 99
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char = t;code = 116
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
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char = i;code = 105
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = p;code = 112
char = 1;code = 49
char = 4;code = 52
char = A;code = 65
char = R;code = 82
char = F;code = 70
char = -;code = 45
char = m;code = 109
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char = d;code = 100
char = i;code = 105
char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = w;code = 119
char = n;code = 110
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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 = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = M;code = 77
char = D;code = 68
char = M;code = 77
char = 2;code = 50
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char = e;code = 101
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char = ,;code = 44
char = ;code = 32
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char = i;code = 105
char = b;code = 98
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char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 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
char = /;code = 47
char = p;code = 112
char = 6;code = 54
char = 5;code = 53
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = c;code = 99
char = r;code = 114
char = i;code = 105
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = a;code = 97
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = c;code = 99
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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 = ;code = 32
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char = d;code = 100
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char = i;code = 105
char = n;code = 110
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char = c;code = 99
char = t;code = 116
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char = o;code = 111
char = n;code = 110
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char = o;code = 111
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char = ;code = 32
char = p;code = 112
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char = A;code = 65
char = F;code = 70
char = -;code = 45
char = 1;code = 49
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char = i;code = 105
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char = ;code = 32
char = d;code = 100
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char = a;code = 97
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char = n;code = 110
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char = A;code = 65
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char = t;code = 116
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char = u;code = 117
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char = e;code = 101
char = d;code = 100
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = R;code = 82
char = O;code = 79
char = S;code = 83
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char = g;code = 103
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char = o;code = 111
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = m;code = 109
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char = t;code = 116
char = o;code = 111
char = c;code = 99
char = h;code = 104
char = o;code = 111
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char = d;code = 100
char = r;code = 114
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char = a;code = 97
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char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = o;code = 111
char = c;code = 99
char = c;code = 99
char = u;code = 117
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
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
char = ;code = 32
char = 1;code = 49
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 3;code = 51
char = ;code = 32
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = f;code = 102
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = p;code = 112
char = i;code = 105
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = t;code = 116
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char = e;code = 101
char = s;code = 115
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 = w;code = 119
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char = r;code = 114
char = e;code = 101
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
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char = b;code = 98
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
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char = p;code = 112
char = r;code = 114
char = e;code = 101
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
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char = o;code = 111
char = f;code = 102
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 = 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 = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = d;code = 100
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = N;code = 78
char = -;code = 45
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = t;code = 116
char = y;code = 121
char = l;code = 108
char = c;code = 99
char = y;code = 121
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = p;code = 112
char = 5;code = 53
char = 3;code = 51
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 = o;code = 111
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = -;code = 45
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 = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = z;code = 122
char = y;code = 121
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = a;code = 97
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = p;code = 112
char = i;code = 105
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = n;code = 110
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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 = p;code = 112
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char = 3;code = 51
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = a;code = 97
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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 = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = u;code = 117
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
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char = a;code = 97
char = t;code = 116
char = t;code = 116
char = e;code = 101
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char = u;code = 117
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 = p;code = 112
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char = 3;code = 51
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = g;code = 103
char = o;code = 111
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char = u;code = 117
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = o;code = 111
char = t;code = 116
char = i;code = 105
char = d;code = 100
char = e;code = 101
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char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
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char = .;code = 46
char = ;code = 32
char = E;code = 69
char = x;code = 120
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = e;code = 101
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
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char = t;code = 116
char = o;code = 111
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char = a;code = 97
char = p;code = 112
char = i;code = 105
char = g;code = 103
char = e;code = 101
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char = n;code = 110
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char = l;code = 108
char = e;code = 101
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char = t;code = 116
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char = a;code = 97
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char = d;code = 100
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char = c;code = 99
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char = e;code = 101
char = a;code = 97
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char = i;code = 105
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char = e;code = 101
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char = e;code = 101
char = l;code = 108
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char = f;code = 102
char = ;code = 32
char = B;code = 66
char = c;code = 99
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char = -;code = 45
char = X;code = 88
char = L;code = 76
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char = a;code = 97
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char = d;code = 100
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char = B;code = 66
char = c;code = 99
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char = 2;code = 50
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char = e;code = 101
char = a;code = 97
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char = a;code = 97
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char = ,;code = 44
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char = t;code = 116
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char = g;code = 103
char = g;code = 103
char = e;code = 101
char = r;code = 114
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char = n;code = 110
char = g;code = 103
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char = c;code = 99
char = a;code = 97
char = s;code = 115
char = p;code = 112
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char = e;code = 101
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char = a;code = 97
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char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
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char = i;code = 105
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char = .;code = 46
char = ;code = 32
char = T;code = 84
char = r;code = 114
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char = a;code = 97
char = t;code = 116
char = m;code = 109
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char = n;code = 110
char = t;code = 116
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char = w;code = 119
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char = t;code = 116
char = h;code = 104
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = c;code = 99
char = a;code = 97
char = s;code = 115
char = p;code = 112
char = a;code = 97
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char = e;code = 101
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char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
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char = r;code = 114
char = s;code = 115
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char = Z;code = 90
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char = V;code = 86
char = A;code = 65
char = D;code = 68
char = -;code = 45
char = F;code = 70
char = M;code = 77
char = K;code = 75
char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = D;code = 68
char = E;code = 69
char = V;code = 86
char = D;code = 68
char = -;code = 45
char = C;code = 67
char = H;code = 72
char = O;code = 79
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char = p;code = 112
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
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char = r;code = 114
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char = s;code = 115
char = c;code = 99
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char = e;code = 101
char = d;code = 100
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char = t;code = 116
char = h;code = 104
char = e;code = 101
char = s;code = 115
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
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char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
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char = a;code = 97
char = p;code = 112
char = i;code = 105
char = g;code = 103
char = e;code = 101
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char = n;code = 110
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char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
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char = e;code = 101
char = d;code = 100
char = ;code = 32
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char = o;code = 111
char = p;code = 112
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char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
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char = v;code = 118
char = i;code = 105
char = v;code = 118
char = o;code = 111
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char = p;code = 112
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char = e;code = 101
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char = t;code = 116
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char = i;code = 105
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char = e;code = 101
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char = s;code = 115
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char = a;code = 97
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char = i;code = 105
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char = 2;code = 50
char = 2;code = 50
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char = u;code = 117
char = m;code = 109
char = o;code = 111
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char = s;code = 115
char = .;code = 46
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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 = u;code = 117
char = l;code = 108
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char = c;code = 99
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char = e;code = 101
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char = t;code = 116
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char = a;code = 97
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char = a;code = 97
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char = i;code = 105
char = g;code = 103
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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 = o;code = 111
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char = t;code = 116
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char = s;code = 115
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char = i;code = 105
char = n;code = 110
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char = 2;code = 50
char = 2;code = 50
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char = v;code = 118
char = 1;code = 49
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
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char = i;code = 105
char = s;code = 115
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char = i;code = 105
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char = i;code = 105
char = t;code = 116
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char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
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char = a;code = 97
char = ;code = 32
char = R;code = 82
char = O;code = 79
char = S;code = 83
char = -;code = 45
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = e;code = 101
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char = d;code = 100
char = e;code = 101
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char = i;code = 105
char = s;code = 115
char = r;code = 114
char = u;code = 117
char = p;code = 112
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
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char = m;code = 109
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = c;code = 99
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char = r;code = 114
char = i;code = 105
char = a;code = 97
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char = m;code = 109
char = e;code = 101
char = m;code = 109
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char = r;code = 114
char = a;code = 97
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char = e;code = 101
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
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char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = c;code = 99
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char = i;code = 105
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = a;code = 97
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char = -;code = 45
char = d;code = 100
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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 = a;code = 97
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result sql = Apigenin, a plant flavone, potentially activates wild-type p53 and induces apoptosis in cancer cells. We conducted detailed studies to understand its mechanism of action. Exposure of human prostate cancer 22Rv1 cells, harboring wild-type p53, to growth-suppressive concentrations (10-80 microM) of apigenin resulted in the stabilization of p53 by phosphorylation on critical serine sites, p14ARF-mediated downregulation of MDM2 protein, inhibition of NF-kappaB/p65 transcriptional activity, and induction of p21/WAF-1 in a dose- and time-dependent manner. Apigenin at these doses resulted in ROS generation, which was accompanied by rapid glutathione depletion, disruption of mitochondrial membrane potential, cytosolic release of cytochrome c, and apoptosis. Interestingly, we observed accumulation of a p53 fraction to the mitochondria, which was rapid and occurred between 1 and 3 h after apigenin treatment. All these effects were significantly blocked by pretreatment of cells with the antioxidant N-acetylcysteine, p53 inhibitor pifithrin-alpha, and enzyme catalase. Apigenin-mediated p53 activation and apoptosis were further attenuated by p53 antisense oligonucleotide treatment. Exposure of cells to apigenin led to a decrease in the levels of Bcl-XL and Bcl-2 and increase in Bax, triggering caspase activation. Treatment with the caspase inhibitors Z-VAD-FMK and DEVD-CHO partially rescued these cells from apigenin-induced apoptosis. In vivo, apigenin administration demonstrated p53-mediated induction of apoptosis in 22Rv1 tumors. These results indicate that apigenin-induced apoptosis in 22Rv1 cells is initiated by a ROS-dependent disruption of the mitochondrial membrane potential through transcriptional-dependent and -independent p53 pathways.

Publication: Free Radic. Biol. Med. 2008 May 15 ;44(10)::1833-45. :doi: 10.1016/j.freeradbiomed.2008.02.007.
Publication Date: 2008 May 15
Study Author(s): Shukla, Sanjeev;Gupta, Sanjay;
Institution: Department of Urology, Case Western Reserve University, Cleveland, OH 44106, USA.
Shortcut link to this study:
Apigenin, a plant flavone, potentially activates wild-type p53 and induces apoptosis in cancer cells. We conducted detailed studies to understand its mechanism of action. Exposure of human prostate cancer 22Rv1 cells, harboring wild-type p53, to growth-suppressive concentrations (10-80 microM) of apigenin resulted in the stabilization of p53 by phosphorylation on critical serine sites, p14ARF-mediated downregulation of MDM2 protein, inhibition of NF-kappaB/p65 transcriptional activity, and induction of p21/WAF-1 in a dose- and time-dependent manner. Apigenin at these doses resulted in ROS generation, which was accompanied by rapid glutathione depletion, disruption of mitochondrial membrane potential, cytosolic release of cytochrome c, and apoptosis. Interestingly, we observed accumulation of a p53 fraction to the mitochondria, which was rapid and occurred between 1 and 3 h after apigenin treatment. All these effects were significantly blocked by pretreatment of cells with the antioxidant N-acetylcysteine, p53 inhibitor pifithrin-alpha, and enzyme catalase. Apigenin-mediated p53 activation and apoptosis were further attenuated by p53 antisense oligonucleotide treatment. Exposure of cells to apigenin led to a decrease in the levels of Bcl-XL and Bcl-2 and increase in Bax, triggering caspase activation. Treatment with the caspase inhibitors Z-VAD-FMK and DEVD-CHO partially rescued these cells from apigenin-induced apoptosis. In vivo, apigenin administration demonstrated p53-mediated induction of apoptosis in 22Rv1 tumors. These results indicate that apigenin-induced apoptosis in 22Rv1 cells is initiated by a ROS-dependent disruption of the mitochondrial membrane potential through transcriptional-dependent and -independent p53 pathways.
PMID: 18342637

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