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result sql = Inorganic selenium sensitizes prostate cancer cells to TRAIL-induced apoptosis through superoxide/p53/Bax-mediated activation of mitochondrial pathway.

Inorganic selenium sensitizes prostate cancer cells to TRAIL-induced apoptosis through superoxide/p53/Bax-mediated activation of mitochondrial pathway.

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char = ;code = 32
char = B;code = 66
char = I;code = 73
char = D;code = 68
char = ;code = 32
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = v;code = 118
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = c;code = 99
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 = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = a;code = 97
char = c;code = 99
char = k;code = 107
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = B;code = 66
char = a;code = 97
char = x;code = 120
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = c;code = 99
char = h;code = 104
char = o;code = 111
char = n;code = 110
char = d;code = 100
char = r;code = 114
char = i;code = 105
char = a;code = 97
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = n;code = 110
char = t;code = 116
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 = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = 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 = c;code = 99
char = a;code = 97
char = s;code = 115
char = c;code = 99
char = a;code = 97
char = d;code = 100
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = e;code = 101
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 = a;code = 97
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 = g;code = 103
char = e;code = 101
char = n;code = 110
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 = s;code = 115
char = u;code = 117
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = d;code = 100
char = e;code = 101
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 = S;code = 83
char = e;code = 101
char = r;code = 114
char = (;code = 40
char = 1;code = 49
char = 5;code = 53
char = );code = 41
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 = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = B;code = 66
char = a;code = 97
char = x;code = 120
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = c;code = 99
char = h;code = 104
char = o;code = 111
char = n;code = 110
char = d;code = 100
char = r;code = 114
char = i;code = 105
char = a;code = 97
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = T;code = 84
char = R;code = 82
char = A;code = 65
char = I;code = 73
char = L;code = 76
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = b;code = 98
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
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 = 32
char = l;code = 108
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = g;code = 103
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = B;code = 66
char = a;code = 97
char = x;code = 120
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = c;code = 99
char = h;code = 104
char = o;code = 111
char = n;code = 110
char = d;code = 100
char = r;code = 114
char = i;code = 105
char = a;code = 97
char = ,;code = 44
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = s;code = 115
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = c;code = 99
char = h;code = 104
char = o;code = 111
char = n;code = 110
char = d;code = 100
char = r;code = 114
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = m;code = 109
char = b;code = 98
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = c;code = 99
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = v;code = 118
char = a;code = 97
char = g;code = 103
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 = 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 = 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 = n;code = 110
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = s;code = 115
char = p;code = 112
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = -;code = 45
char = 3;code = 51
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 = n;code = 110
char = g;code = 103
char = ;code = 32
char = p;code = 112
char = 5;code = 53
char = 3;code = 51
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = -;code = 45
char = n;code = 110
char = e;code = 101
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = s;code = 115
char = h;code = 104
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 = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
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 = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = u;code = 117
char = t;code = 116
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
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 = 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 = 44
char = ;code = 32
char = B;code = 66
char = a;code = 97
char = x;code = 120
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = c;code = 99
char = h;code = 104
char = o;code = 111
char = n;code = 110
char = d;code = 100
char = r;code = 114
char = i;code = 105
char = a;code = 97
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = c;code = 99
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
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 = 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 = b;code = 98
char = y;code = 121
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = /;code = 47
char = T;code = 84
char = R;code = 82
char = A;code = 65
char = I;code = 73
char = L;code = 76
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = p;code = 112
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = B;code = 66
char = a;code = 97
char = x;code = 120
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = c;code = 99
char = r;code = 114
char = u;code = 117
char = c;code = 99
char = i;code = 105
char = a;code = 97
char = l;code = 108
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 = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = s;code = 115
char = -;code = 45
char = t;code = 116
char = a;code = 97
char = l;code = 108
char = k;code = 107
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 = s;code = 115
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = T;code = 84
char = R;code = 82
char = A;code = 65
char = I;code = 73
char = L;code = 76
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 = s;code = 115
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = 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 = 97
char = x;code = 120
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = p;code = 112
char = 5;code = 53
char = 3;code = 51
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = t;code = 116
char = a;code = 97
char = n;code = 110
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char = t;code = 116
char = ;code = 32
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char = l;code = 108
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char = n;code = 110
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char = t;code = 116
char = e;code = 101
char = ;code = 32
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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 = s;code = 115
char = ;code = 32
char = a;code = 97
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char = c;code = 99
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char = l;code = 108
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char = n;code = 110
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char = ;code = 32
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char = r;code = 114
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char = ;code = 32
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char = o;code = 111
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result sql = Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to induce apoptosis in prostate cancer cells through DR4 and DR5 death receptors, but not in normal prostate cells, which do not express these receptors. Therefore, TRAIL has excellent potential to be a selective prostate cancer therapeutic agent with minimal toxic side effects. However, prostate cancer cells, as many other cancer types, develop resistance to TRAIL, and the underlying molecular mechanisms require further investigation. We hypothesize that selenium may sensitize TRAIL-resistant cells to undergo caspase-mediated apoptosis and increase therapeutic efficacy. Here, we report that TRAIL signaling in LNCaP prostate cancer cells stalled at downstream of caspase-8 and BID cleavage, as indicated by the lack of Bax translocation into mitochondria, and no subsequent activation of the caspase-9 cascade. Selenite induced a rapid generation of superoxide and p53 Ser(15) phosphorylation and increased Bax abundance and translocation into the mitochondria. Selenite and TRAIL combined treatment led to synergistic increases of Bax abundance and translocation into mitochondria, loss of mitochondrial membrane potential, cytochrome c release, and cleavage activation of caspase-9 and caspase-3. Inactivating p53 with a dominant-negative mutant abolished apoptosis without affecting superoxide generation, whereas a superoxide dismutase mimetic agent blocked p53 activation, Bax translocation to mitochondria, cytochrome c release, and apoptosis induced by selenite/TRAIL. In support of Bax as a crucial target for cross-talk between selenite and TRAIL pathways, introduction of Bax into p53 mutant DU145 cells enabled selenite to sensitize these cells for TRAIL-induced apoptosis. Taken together, the results indicate that selenite induces a rapid superoxide burst and p53 activation, leading to Bax up-regulation and translocation into mitochondria, which restores the cross-talk with stalled TRAIL signaling for a synergistic caspase-9/3 cascade-mediated apoptosis execution.

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