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result sql = Plant flavonoid apigenin inactivates Akt to trigger apoptosis in human prostate cancer: an in vitro and in vivo study.

Plant flavonoid apigenin inactivates Akt to trigger apoptosis in human prostate cancer: an in vitro and in vivo study.

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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 = o;code = 111
char = f;code = 102
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = k;code = 107
char = i;code = 105
char = n;code = 110
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 = 44
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 = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = f;code = 102
char = i;code = 105
char = r;code = 114
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = r;code = 114
char = e;code = 101
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 = h;code = 104
char = o;code = 111
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = r;code = 114
char = y;code = 121
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 = p;code = 112
char = r;code = 114
char = o;code = 111
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 = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = B;code = 66
char = A;code = 65
char = D;code = 68
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = g;code = 103
char = l;code = 108
char = y;code = 121
char = c;code = 99
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = -;code = 45
char = 3;code = 51
char = ,;code = 44
char = ;code = 32
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
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 = t;code = 116
char = a;code = 97
char = r;code = 114
char = g;code = 103
char = e;code = 101
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = A;code = 65
char = k;code = 107
char = t;code = 116
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = y;code = 121
char = p;code = 112
char = o;code = 111
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 = r;code = 114
char = y;code = 121
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 = A;code = 65
char = D;code = 68
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = 1;code = 49
char = 4;code = 52
char = -;code = 45
char = 3;code = 51
char = -;code = 45
char = 3;code = 51
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
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 = 2;code = 50
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 = 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 = e;code = 101
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
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = P;code = 80
char = C;code = 67
char = -;code = 45
char = 3;code = 51
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 = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = 2;code = 50
char = 4;code = 52
char = ;code = 32
char = h;code = 104
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
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 = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = A;code = 65
char = k;code = 107
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = e;code = 101
char = m;code = 109
char = s;code = 115
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 = 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 = 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 = i;code = 105
char = n;code = 110
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = -;code = 45
char = l;code = 108
char = i;code = 105
char = k;code = 107
char = e;code = 101
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = 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 = 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 = 1;code = 49
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
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 = 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 = o;code = 111
char = f;code = 102
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = u;code = 117
char = t;code = 116
char = o;code = 111
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 = r;code = 114
char = y;code = 121
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 = u;code = 117
char = p;code = 112
char = o;code = 111
char = n;code = 110
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 = 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
char = ;code = 32
char = t;code = 116
char = o;code = 111
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 = 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 = 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 = 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 = 9;code = 57
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 = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = d;code = 100
char = e;code = 101
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 = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = v;code = 118
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = P;code = 80
char = C;code = 67
char = -;code = 45
char = 3;code = 51
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
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = s;code = 115
char = e;code = 101
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 = m;code = 109
char = a;code = 97
char = n;code = 110
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = .;code = 46
char = ;code = 32
char = F;code = 70
char = u;code = 117
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = S;code = 83
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = 4;code = 52
char = 7;code = 55
char = 3;code = 51
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 = r;code = 114
char = y;code = 121
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 = e;code = 101
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = p;code = 112
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = e;code = 101
char = x;code = 120
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 = d;code = 100
char = ;code = 32
char = A;code = 65
char = k;code = 107
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = D;code = 68
char = U;code = 85
char = 1;code = 49
char = 4;code = 52
char = 5;code = 53
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 = a;code = 97
char = s;code = 115
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 = r;code = 114
char = e;code = 101
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = u;code = 117
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = 2;code = 50
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 = 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 = I;code = 73
char = n;code = 110
char = ;code = 32
char = v;code = 118
char = i;code = 105
char = v;code = 118
char = o;code = 111
char = ,;code = 44
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 = i;code = 105
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = k;code = 107
char = e;code = 101
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 = g;code = 103
char = a;code = 97
char = v;code = 118
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
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 = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = A;code = 65
char = k;code = 107
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 = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
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 = 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 = P;code = 80
char = C;code = 67
char = -;code = 45
char = 3;code = 51
char = ;code = 32
char = t;code = 116
char = u;code = 117
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = s;code = 115
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
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = s;code = 115
char = ;code = 32
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
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result sql = Inappropriate activation of phosphatidylinositol 3-kinase-Akt signaling contributes to the development of several human malignancies. Modulation of Akt activity is a strategy that may be valuable in chemopreventive and chemotherapeutic regimens. We have previously demonstrated that apigenin, a plant flavone, causes decreased survival in human prostate cancer cells. However, the molecular mechanism underlying this observation remains elusive. In the present study, we investigated the mechanisms of apigenin action on human prostate cancer PC-3 cells, which possess constitutively active Akt. Treatment of PC-3 cells with apigenin (5-40 microM) resulted in significant dose- and time-dependent decrease in Akt phosphorylation at Serine473. Apigenin-mediated dephosphorylation of Akt resulted in inhibition of its kinase activity, which was confirmed by reduced phosphorylation of proapoptotic proteins BAD and glycogen synthase kinase-3, essential downstream targets of Akt. Hypophosphorylation of BAD resulted in reduced interaction with 14-3-3beta protein after 20 microM apigenin exposure to PC-3 cells for 24 h. Inactivation of Akt seems to be associated with downregulation of insulin-like growth factor receptor 1 protein level and inhibition of its autophosphorylation upon apigenin treatment. Exposure to apigenin significantly induced caspase-9 activity and decreased the survival of PC-3 cells in a dose-dependent manner. Furthermore, Serine473 phosphorylation of ectopically expressed Akt in DU145 cells was significantly reduced upon 20 microM apigenin treatment. In vivo, apigenin intake through gavage resulted in inactivation of Akt and induction of apoptosis in PC-3 tumors. These results suggest that Akt inactivation and dephosphorylation of BAD is a critical event, at least in part, in apigenin-induced decreased cell survival and apoptosis.

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