|
|
char = L;code = 76
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char = m;code = 109
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char = t;code = 116
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char = R;code = 82
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char = s;code = 115
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char = .;code = 46
result sql = Lycopene induces cell growth inhibition by altering mevalonate pathway and Ras signaling in cancer cell lines.
Lycopene induces cell growth inhibition by altering mevalonate pathway and Ras signaling in cancer cell lines.char = S;code = 83
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char = a;code = 97
char = t;code = 116
char = a;code = 97
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char = e;code = 101
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 = 46
char = ;code = 32
char = T;code = 84
char = o;code = 111
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char = a;code = 97
char = t;code = 116
char = o;code = 111
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char = l;code = 108
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char = f;code = 102
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char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = c;code = 99
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char = e;code = 101
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char = n;code = 110
char = t;code = 116
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char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = l;code = 108
char = y;code = 121
char = c;code = 99
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char = p;code = 112
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char = n;code = 110
char = e;code = 101
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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
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char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = R;code = 82
char = a;code = 97
char = s;code = 115
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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
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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 = o;code = 111
char = f;code = 102
char = ;code = 32
char = n;code = 110
char = u;code = 117
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = r;code = 114
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 = 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 = 32
char = (;code = 40
char = N;code = 78
char = F;code = 70
char = -;code = 45
char = ?;code = 63
char = B;code = 66
char = );code = 41
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = u;code = 117
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = r;code = 114
char = e;code = 101
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 = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = a;code = 97
char = n;code = 110
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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
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char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
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 = p;code = 112
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 = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = a;code = 97
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
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = 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 = c;code = 99
char = -;code = 45
char = j;code = 106
char = u;code = 117
char = n;code = 110
char = ;code = 32
char = N;code = 78
char = -;code = 45
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = 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 = 44
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
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 = -;code = 45
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
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 = 1;code = 49
char = /;code = 47
char = 2;code = 50
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = 3;code = 51
char = 8;code = 56
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
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char = 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 = a;code = 97
char = l;code = 108
char = s;code = 115
char = o;code = 111
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char = a;code = 97
char = c;code = 99
char = c;code = 99
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char = m;code = 109
char = p;code = 112
char = a;code = 97
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char = i;code = 105
char = e;code = 101
char = d;code = 100
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char = b;code = 98
char = y;code = 121
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char = a;code = 97
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
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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
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char = p;code = 112
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
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char = a;code = 97
char = p;code = 112
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 = s;code = 115
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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
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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 = e;code = 101
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char = a;code = 97
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char = i;code = 105
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char = ;code = 32
char = c;code = 99
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = i;code = 105
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char = D;code = 68
char = 1;code = 49
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char = a;code = 97
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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 = A;code = 65
char = K;code = 75
char = T;code = 84
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
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 = d;code = 100
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char = b;code = 98
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char = a;code = 97
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char = i;code = 105
char = n;code = 110
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char = e;code = 101
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char = p;code = 112
char = 2;code = 50
char = 1;code = 49
char = ,;code = 44
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char = p;code = 112
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char = 7;code = 55
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = p;code = 112
char = 5;code = 53
char = 3;code = 51
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char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
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char = s;code = 115
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char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
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char = B;code = 66
char = a;code = 97
char = x;code = 120
char = :;code = 58
char = B;code = 66
char = c;code = 99
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char = -;code = 45
char = 2;code = 50
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char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
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char = a;code = 97
char = d;code = 100
char = d;code = 100
char = i;code = 105
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
char = m;code = 109
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char = v;code = 118
char = a;code = 97
char = l;code = 108
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 = p;code = 112
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = n;code = 110
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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
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char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
char = -;code = 45
char = i;code = 105
char = n;code = 110
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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 = y;code = 121
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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 = o;code = 111
char = f;code = 102
char = ;code = 32
char = l;code = 108
char = y;code = 121
char = c;code = 99
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char = p;code = 112
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char = n;code = 110
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = s;code = 115
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char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = R;code = 82
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = m;code = 109
char = a;code = 97
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char = i;code = 105
char = c;code = 99
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char = a;code = 97
char = c;code = 99
char = c;code = 99
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char = m;code = 109
char = u;code = 117
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 = a;code = 97
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char = h;code = 104
char = e;code = 101
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char = s;code = 115
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char = b;code = 98
char = s;code = 115
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char = q;code = 113
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char = e;code = 101
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char = g;code = 103
char = e;code = 101
char = s;code = 115
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char = i;code = 105
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char = N;code = 78
char = F;code = 70
char = -;code = 45
char = ?;code = 63
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char = .;code = 46
char = ;code = 32
char = T;code = 84
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char = e;code = 101
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char = a;code = 97
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char = i;code = 105
char = b;code = 98
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char = t;code = 116
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char = ;code = 32
char = H;code = 72
char = M;code = 77
char = G;code = 71
char = -;code = 45
char = C;code = 67
char = o;code = 111
char = A;code = 65
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char = r;code = 114
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char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
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char = s;code = 115
char = s;code = 115
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char = o;code = 111
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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 = l;code = 108
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char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
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char = i;code = 105
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char = i;code = 105
char = n;code = 110
char = a;code = 97
char = c;code = 99
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char = i;code = 105
char = v;code = 118
char = a;code = 97
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char = n;code = 110
char = g;code = 103
char = ;code = 32
char = R;code = 82
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = o;code = 111
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char = f;code = 102
char = o;code = 111
char = u;code = 117
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char = i;code = 105
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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
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char = P;code = 80
char = C;code = 67
char = -;code = 45
char = 3;code = 51
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = l;code = 108
char = o;code = 111
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char = ;code = 32
char = H;code = 72
char = C;code = 67
char = T;code = 84
char = -;code = 45
char = 1;code = 49
char = 1;code = 49
char = 6;code = 54
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = H;code = 72
char = T;code = 84
char = -;code = 45
char = 2;code = 50
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = l;code = 108
char = u;code = 117
char = n;code = 110
char = g;code = 103
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char = B;code = 66
char = E;code = 69
char = N;code = 78
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
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
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
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char = f;code = 102
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = n;code = 110
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char = s;code = 115
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char = p;code = 112
char = r;code = 114
char = o;code = 111
char = v;code = 118
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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 = n;code = 110
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = l;code = 108
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char = i;code = 105
char = n;code = 110
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char = o;code = 111
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char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = g;code = 103
char = r;code = 114
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char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
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char = y;code = 121
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char = f;code = 102
char = f;code = 102
char = e;code = 101
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char = c;code = 99
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char = n;code = 110
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char = r;code = 114
char = .;code = 46
result sql = Several evidences suggest that cancer cells have abnormal cholesterol biosynthetic pathways and prenylation of small guanosine triphosphatase proteins. Tomato lycopene has been suggested to have beneficial effects against certain types of cancer, including that of prostate, although the exact molecular mechanism(s) is unknown. We tested the hypothesis that lycopene may exert its antitumor effects through changes in mevalonate pathway and in Ras activation. Incubation of the Ras-activated prostatic carcinoma LNCaP cells with a 24 h lycopene treatment (2.5-10 μM) dose dependently reduced intracellular total cholesterol by decreasing 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase expression and by inactivating Ras, as evidenced by its translocation from cell membranes to cytosol. Concomitantly, lycopene reduced the Ras-dependent activation of nuclear factor-kappaB (NF-?B). Such a reduction was parallel to an inhibition of reactive oxygen species production and to a decrease in the phosphorylation ofc-jun N-terminal kinase, extracellular signal-regulated kinase 1/2 and p38. These effects were also accompanied by an arrest of cell cycle progression and by apoptosis induction, as evidenced by a decrease in cyclin D1 and phospho-AKT levels and by an increase in p21, p27 and p53 levels and in Bax:Bcl-2 ratio. The addition of mevalonate prevented the growth-inhibitory effects of lycopene as well as its increase in Ras cytoplasmatic accumulation and the subsequent changes in NF-?B. The ability of lycopene in inhibiting HMG-CoA reductase expression and cell growth and in inactivating Ras was also found in prostate PC-3, colon HCT-116 and HT-29 and lung BEN cancer cells. These findings provide a novel mechanistic insight into the growth-inhibitory effects of lycopene in cancer.
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char = e;code = 101
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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
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
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 = i;code = 105
char = n;code = 110
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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
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char = b;code = 98
char = y;code = 121
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char = a;code = 97
char = l;code = 108
char = t;code = 116
char = e;code = 101
char = r;code = 114
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char = n;code = 110
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char = m;code = 109
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char = d;code = 100
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char = s;code = 115
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char = i;code = 105
char = n;code = 110
char = g;code = 103
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char = i;code = 105
char = n;code = 110
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
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char = c;code = 99
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char = l;code = 108
char = l;code = 108
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = .;code = 46
result sql = Lycopene induces cell growth inhibition by altering mevalonate pathway and Ras signaling in cancer cell lines.
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char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
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char = s;code = 115
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
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char = s;code = 115
char = s;code = 115
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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 = b;code = 98
char = y;code = 121
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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 = n;code = 110
char = g;code = 103
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char = R;code = 82
char = a;code = 97
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = s;code = 115
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char = e;code = 101
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char = i;code = 105
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
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char = ;code = 32
char = i;code = 105
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = 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 = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
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char = c;code = 99
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char = l;code = 108
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 = s;code = 115
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char = t;code = 116
char = o;code = 111
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = o;code = 111
char = l;code = 108
char = .;code = 46
char = ;code = 32
char = C;code = 67
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = i;code = 105
char = t;code = 116
char = a;code = 97
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char = t;code = 116
char = l;code = 108
char = y;code = 121
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char = ;code = 32
char = l;code = 108
char = y;code = 121
char = c;code = 99
char = o;code = 111
char = p;code = 112
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char = n;code = 110
char = e;code = 101
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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 = t;code = 116
char = h;code = 104
char = e;code = 101
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char = R;code = 82
char = a;code = 97
char = s;code = 115
char = -;code = 45
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = 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 = n;code = 110
char = u;code = 117
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = r;code = 114
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 = 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 = 32
char = (;code = 40
char = N;code = 78
char = F;code = 70
char = -;code = 45
char = ?;code = 63
char = B;code = 66
char = );code = 41
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = u;code = 117
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = r;code = 114
char = e;code = 101
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 = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = a;code = 97
char = n;code = 110
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 = 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 = p;code = 112
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 = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
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char = a;code = 97
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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
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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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 = c;code = 99
char = -;code = 45
char = j;code = 106
char = u;code = 117
char = n;code = 110
char = ;code = 32
char = N;code = 78
char = -;code = 45
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = k;code = 107
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char = n;code = 110
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = e;code = 101
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char = t;code = 116
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
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 = -;code = 45
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
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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 = 1;code = 49
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char = 2;code = 50
char = ;code = 32
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char = d;code = 100
char = ;code = 32
char = p;code = 112
char = 3;code = 51
char = 8;code = 56
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
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char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
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char = t;code = 116
char = s;code = 115
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char = r;code = 114
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 = c;code = 99
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char = a;code = 97
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char = i;code = 105
char = e;code = 101
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char = b;code = 98
char = y;code = 121
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char = a;code = 97
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char = ;code = 32
char = a;code = 97
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = t;code = 116
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
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char = l;code = 108
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = y;code = 121
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char = l;code = 108
char = e;code = 101
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char = p;code = 112
char = r;code = 114
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char = g;code = 103
char = r;code = 114
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char = s;code = 115
char = s;code = 115
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char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = b;code = 98
char = y;code = 121
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char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
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char = o;code = 111
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char = s;code = 115
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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
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char = ,;code = 44
char = ;code = 32
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char = e;code = 101
char = v;code = 118
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char = a;code = 97
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char = e;code = 101
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
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char = e;code = 101
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char = ;code = 32
char = c;code = 99
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = D;code = 68
char = 1;code = 49
char = ;code = 32
char = a;code = 97
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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 = -;code = 45
char = A;code = 65
char = K;code = 75
char = T;code = 84
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
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char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
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char = a;code = 97
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = i;code = 105
char = n;code = 110
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char = p;code = 112
char = 2;code = 50
char = 1;code = 49
char = ,;code = 44
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char = p;code = 112
char = 2;code = 50
char = 7;code = 55
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 = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = B;code = 66
char = a;code = 97
char = x;code = 120
char = :;code = 58
char = B;code = 66
char = c;code = 99
char = l;code = 108
char = -;code = 45
char = 2;code = 50
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char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
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char = a;code = 97
char = d;code = 100
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = t;code = 116
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 = e;code = 101
char = n;code = 110
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char = h;code = 104
char = e;code = 101
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char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
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char = h;code = 104
char = -;code = 45
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char = i;code = 105
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char = t;code = 116
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char = y;code = 121
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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 = o;code = 111
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char = c;code = 99
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char = n;code = 110
char = e;code = 101
char = ;code = 32
char = a;code = 97
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char = ;code = 32
char = w;code = 119
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char = l;code = 108
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char = a;code = 97
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char = c;code = 99
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char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = i;code = 105
char = n;code = 110
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char = R;code = 82
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
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char = l;code = 108
char = a;code = 97
char = s;code = 115
char = m;code = 109
char = a;code = 97
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char = i;code = 105
char = c;code = 99
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char = a;code = 97
char = c;code = 99
char = c;code = 99
char = u;code = 117
char = m;code = 109
char = u;code = 117
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 = a;code = 97
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char = d;code = 100
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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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
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char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = g;code = 103
char = e;code = 101
char = s;code = 115
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = N;code = 78
char = F;code = 70
char = -;code = 45
char = ?;code = 63
char = B;code = 66
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = l;code = 108
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char = c;code = 99
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char = p;code = 112
char = e;code = 101
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char = i;code = 105
char = n;code = 110
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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
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char = n;code = 110
char = g;code = 103
char = ;code = 32
char = H;code = 72
char = M;code = 77
char = G;code = 71
char = -;code = 45
char = C;code = 67
char = o;code = 111
char = A;code = 65
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = s;code = 115
char = e;code = 101
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 = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
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 = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
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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 = n;code = 110
char = g;code = 103
char = ;code = 32
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result sql = Several evidences suggest that cancer cells have abnormal cholesterol biosynthetic pathways and prenylation of small guanosine triphosphatase proteins. Tomato lycopene has been suggested to have beneficial effects against certain types of cancer, including that of prostate, although the exact molecular mechanism(s) is unknown. We tested the hypothesis that lycopene may exert its antitumor effects through changes in mevalonate pathway and in Ras activation. Incubation of the Ras-activated prostatic carcinoma LNCaP cells with a 24 h lycopene treatment (2.5-10 μM) dose dependently reduced intracellular total cholesterol by decreasing 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase expression and by inactivating Ras, as evidenced by its translocation from cell membranes to cytosol. Concomitantly, lycopene reduced the Ras-dependent activation of nuclear factor-kappaB (NF-?B). Such a reduction was parallel to an inhibition of reactive oxygen species production and to a decrease in the phosphorylation ofc-jun N-terminal kinase, extracellular signal-regulated kinase 1/2 and p38. These effects were also accompanied by an arrest of cell cycle progression and by apoptosis induction, as evidenced by a decrease in cyclin D1 and phospho-AKT levels and by an increase in p21, p27 and p53 levels and in Bax:Bcl-2 ratio. The addition of mevalonate prevented the growth-inhibitory effects of lycopene as well as its increase in Ras cytoplasmatic accumulation and the subsequent changes in NF-?B. The ability of lycopene in inhibiting HMG-CoA reductase expression and cell growth and in inactivating Ras was also found in prostate PC-3, colon HCT-116 and HT-29 and lung BEN cancer cells. These findings provide a novel mechanistic insight into the growth-inhibitory effects of lycopene in cancer.
Publication: Carcinogenesis 2010 Oct ;31(10)::1813-21.
Publication Date: 2010 Oct
Study Author(s): Palozza, Paola;Colangelo, Maria;Simone, Rossella;Catalano, Assunta;Boninsegna, Alma;Lanza, Paola;Monego, Giovanni;Ranelletti, Franco O;
Institution: Institute of General Pathology, Catholic University School of Medicine, L. Go F. Vito, 00168 Rome, Italy. [email protected]
Shortcut link to this study:
Publication Date: 2010 Oct
Study Author(s): Palozza, Paola;Colangelo, Maria;Simone, Rossella;Catalano, Assunta;Boninsegna, Alma;Lanza, Paola;Monego, Giovanni;Ranelletti, Franco O;
Institution: Institute of General Pathology, Catholic University School of Medicine, L. Go F. Vito, 00168 Rome, Italy. [email protected]
Shortcut link to this study:
Several evidences suggest that cancer cells have abnormal cholesterol biosynthetic pathways and prenylation of small guanosine triphosphatase proteins. Tomato lycopene has been suggested to have beneficial effects against certain types of cancer, including that of prostate, although the exact molecular mechanism(s) is unknown. We tested the hypothesis that lycopene may exert its antitumor effects through changes in mevalonate pathway and in Ras activation. Incubation of the Ras-activated prostatic carcinoma LNCaP cells with a 24 h lycopene treatment (2.5-10 μM) dose dependently reduced intracellular total cholesterol by decreasing 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase expression and by inactivating Ras, as evidenced by its translocation from cell membranes to cytosol. Concomitantly, lycopene reduced the Ras-dependent activation of nuclear factor-kappaB (NF-?B). Such a reduction was parallel to an inhibition of reactive oxygen species production and to a decrease in the phosphorylation ofc-jun N-terminal kinase, extracellular signal-regulated kinase 1/2 and p38. These effects were also accompanied by an arrest of cell cycle progression and by apoptosis induction, as evidenced by a decrease in cyclin D1 and phospho-AKT levels and by an increase in p21, p27 and p53 levels and in Bax:Bcl-2 ratio. The addition of mevalonate prevented the growth-inhibitory effects of lycopene as well as its increase in Ras cytoplasmatic accumulation and the subsequent changes in NF-?B. The ability of lycopene in inhibiting HMG-CoA reductase expression and cell growth and in inactivating Ras was also found in prostate PC-3, colon HCT-116 and HT-29 and lung BEN cancer cells. These findings provide a novel mechanistic insight into the growth-inhibitory effects of lycopene in cancer.
PMID: 20699249
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