char = G;code = 71
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = i;code = 105
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = -;code = 45
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = o;code = 111
char = n;code = 110
char = e;code = 101
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 = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = 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 = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
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 = 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 = 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 = 2;code = 50
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 = i;code = 105
char = n;code = 110
char = ;code = 32
char = M;code = 77
char = C;code = 67
char = F;code = 70
char = -;code = 45
char = 7;code = 55
char = ;code = 32
char = b;code = 98
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
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
char = ;code = 32
char = o;code = 111
char = n;code = 110
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 = 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 = 46
result sql = Geraniol and beta-ionone inhibit proliferation, cell cycle progression, and cyclin-dependent kinase 2 activity in MCF-7 breast cancer cells independent of effects on HMG-CoA reductase activity.
Geraniol and beta-ionone inhibit proliferation, cell cycle progression, and cyclin-dependent kinase 2 activity in MCF-7 breast cancer cells independent of effects on HMG-CoA reductase activity.
char = 3;code = 51
char = -;code = 45
char = h;code = 104
char = y;code = 121
char = d;code = 100
char = r;code = 114
char = o;code = 111
char = x;code = 120
char = y;code = 121
char = -;code = 45
char = 3;code = 51
char = -;code = 45
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = y;code = 121
char = l;code = 108
char = g;code = 103
char = l;code = 108
char = u;code = 117
char = t;code = 116
char = a;code = 97
char = r;code = 114
char = y;code = 121
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = e;code = 101
char = n;code = 110
char = z;code = 122
char = y;code = 121
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = A;code = 65
char = ;code = 32
char = (;code = 40
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 = 41
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 = c;code = 99
char = a;code = 97
char = t;code = 116
char = a;code = 97
char = l;code = 108
char = y;code = 121
char = z;code = 122
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = m;code = 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
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = u;code = 117
char = r;code = 114
char = s;code = 115
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = o;code = 111
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = i;code = 105
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = M;code = 77
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
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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 = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = G;code = 71
char = 1;code = 49
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = r;code = 114
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
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = i;code = 105
char = r;code = 114
char = e;code = 101
char = d;code = 100
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 = o;code = 111
char = f;code = 102
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 = 45
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = e;code = 101
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char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
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 = (;code = 40
char = C;code = 67
char = D;code = 68
char = K;code = 75
char = );code = 41
char = ;code = 32
char = 2;code = 50
char = ,;code = 44
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 = 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 = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
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 = o;code = 111
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = G;code = 71
char = 1;code = 49
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = S;code = 83
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
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 = 46
char = ;code = 32
char = I;code = 73
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 = 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
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = f;code = 102
char = u;code = 117
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = g;code = 103
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = i;code = 105
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
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 = o;code = 111
char = f;code = 102
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = n;code = 110
char = t;code = 116
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 = 46
char = ;code = 32
char = P;code = 80
char = l;code = 108
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = p;code = 112
char = r;code = 114
char = e;code = 101
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char = o;code = 111
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char = d;code = 100
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = i;code = 105
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char = c;code = 99
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char = u;code = 117
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
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char = b;code = 98
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char = t;code = 116
char = a;code = 97
char = -;code = 45
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char = o;code = 111
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char = e;code = 101
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = i;code = 105
char = o;code = 111
char = l;code = 108
char = ,;code = 44
char = ;code = 32
char = h;code = 104
char = a;code = 97
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char = e;code = 101
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char = p;code = 112
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = i;code = 105
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = e;code = 101
char = n;code = 110
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char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = o;code = 111
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 = ;code = 32
char = r;code = 114
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char = d;code = 100
char = e;code = 101
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char = ;code = 32
char = m;code = 109
char = a;code = 97
char = m;code = 109
char = m;code = 109
char = a;code = 97
char = r;code = 114
char = y;code = 121
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char = t;code = 116
char = u;code = 117
char = m;code = 109
char = o;code = 111
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char = d;code = 100
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char = l;code = 108
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char = ,;code = 44
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char = d;code = 100
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char = a;code = 97
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char = a;code = 97
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char = ;code = 32
char = h;code = 104
char = e;code = 101
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = c;code = 99
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
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char = d;code = 100
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char = c;code = 99
char = t;code = 116
char = a;code = 97
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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 = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
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char = h;code = 104
char = y;code = 121
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char = o;code = 111
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char = z;code = 122
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char = t;code = 116
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char = a;code = 97
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = u;code = 117
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
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char = e;code = 101
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char = l;code = 108
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char = c;code = 99
char = l;code = 108
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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 = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
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char = o;code = 111
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char = a;code = 97
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char = a;code = 97
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char = o;code = 111
char = l;code = 108
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char = o;code = 111
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char = M;code = 77
char = C;code = 67
char = F;code = 70
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char = h;code = 104
char = u;code = 117
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char = a;code = 97
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char = b;code = 98
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char = e;code = 101
char = a;code = 97
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char = c;code = 99
char = a;code = 97
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char = c;code = 99
char = e;code = 101
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char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
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char = i;code = 105
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char = t;code = 116
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char = a;code = 97
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char = a;code = 97
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char = d;code = 100
char = e;code = 101
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = r;code = 114
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char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
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char = n;code = 110
char = g;code = 103
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char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
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char = i;code = 105
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char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
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char = o;code = 111
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char = o;code = 111
char = f;code = 102
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
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char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = a;code = 97
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char = e;code = 101
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char = a;code = 97
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char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
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char = ;code = 32
char = F;code = 70
char = l;code = 108
char = o;code = 111
char = w;code = 119
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char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = r;code = 114
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char = c;code = 99
char = ;code = 32
char = a;code = 97
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char = a;code = 97
char = l;code = 108
char = y;code = 121
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char = i;code = 105
char = s;code = 115
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char = s;code = 115
char = h;code = 104
char = o;code = 111
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
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char = G;code = 71
char = 1;code = 49
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char = a;code = 97
char = r;code = 114
char = r;code = 114
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char = s;code = 115
char = t;code = 116
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char = i;code = 105
char = s;code = 115
char = o;code = 111
char = p;code = 112
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char = n;code = 110
char = o;code = 111
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char = d;code = 100
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char = t;code = 116
char = r;code = 114
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char = a;code = 97
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char = e;code = 101
char = d;code = 100
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char = M;code = 77
char = C;code = 67
char = F;code = 70
char = -;code = 45
char = 7;code = 55
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char = r;code = 114
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char = h;code = 104
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 = s;code = 115
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char = p;code = 112
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char = o;code = 111
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char = T;code = 84
char = h;code = 104
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char = s;code = 115
char = e;code = 101
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char = l;code = 108
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char = C;code = 67
char = D;code = 68
char = K;code = 75
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char = E;code = 69
char = ,;code = 44
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char = ;code = 32
char = C;code = 67
char = D;code = 68
char = K;code = 75
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char = a;code = 97
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char = w;code = 119
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char = h;code = 104
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char = e;code = 101
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char = s;code = 115
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char = k;code = 107
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char = p;code = 112
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char = o;code = 111
char = A;code = 65
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char = v;code = 118
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char = a;code = 97
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char = 9;code = 57
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char = P;code = 80
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char = <;code = 60
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char = 0;code = 48
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char = e;code = 101
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char = e;code = 101
char = s;code = 115
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char = o;code = 111
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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 = i;code = 105
char = n;code = 110
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = i;code = 105
char = o;code = 111
char = l;code = 108
char = -;code = 45
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 = e;code = 101
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = e;code = 101
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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
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
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 = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = i;code = 105
char = r;code = 114
char = e;code = 101
char = d;code = 100
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
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char = e;code = 101
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = -;code = 45
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = 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 = o;code = 111
char = r;code = 114
char = y;code = 121
char = ;code = 32
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
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = -;code = 45
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = i;code = 105
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = h;code = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
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result sql = 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase catalyzes the formation of mevalonate, a precursor of cholesterol that is also required for cell proliferation. Mevalonate depletion results in a G1 phase cell cycle arrest that is mediated in part by impaired activity of cyclin-dependent kinase (CDK) 2, and decreased expression of positive regulators of G1 to S phase progression. Inhibition of mevalonate synthesis may, therefore, be a useful strategy to impair the growth of malignant cells. Plant isoprenoids, including beta-ionone and geraniol, have previously been shown to inhibit rodent mammary tumor development, and rodent and avian hepatic HMG-CoA reductase activity. We hypothesized that the putative anti-proliferative and cell cycle inhibitory effects of beta-ionone and geraniol on MCF-7 human breast cancer cells in culture are mediated by mevalonate depletion resulting from inhibition of HMG-CoA reductase activity. Flow cytometric analysis showed a G1 arrest in isoprenoid-treated MCF-7 cells, and also a G2/M arrest at higher concentrations of isoprenoids. These compounds minimally affected the growth of MCF-10F normal breast epithelial cells. Both beta-ionone and geraniol inhibited CDK 2 activity and dose-dependently decreased the expression of cyclins D1, E, and A, and CDK 2 and 4, without changing the expression of p21cip1 or p27kip1. Although both beta-ionone and geraniol also inhibited MCF-7 proliferation, only geraniol inhibited HMG-CoA reductase activity. While these effects were significantly correlated (r2=0.89, P <0.01), they were not causally related, since exogenous mevalonate did not restore growth in geraniol-inhibited cells. These findings indicate that mechanisms other than impaired mevalonate synthesis mediate the anti-proliferative and cell cycle regulatory effects of beta-ionone and geraniol in human breast cancer cells.

Publication: Biochem. Pharmacol. 2004 Nov 1 ;68(9)::1739-47.
Publication Date: 2004 Nov 1
Study Author(s): Duncan, Robin E;Lau, Dominic;El-Sohemy, Ahmed;Archer, Michael C;
Institution: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Fitzgerald Building, 150 College Street, Toronto, Ont., Canada M5S 3E2.
Shortcut link to this study:
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase catalyzes the formation of mevalonate, a precursor of cholesterol that is also required for cell proliferation. Mevalonate depletion results in a G1 phase cell cycle arrest that is mediated in part by impaired activity of cyclin-dependent kinase (CDK) 2, and decreased expression of positive regulators of G1 to S phase progression. Inhibition of mevalonate synthesis may, therefore, be a useful strategy to impair the growth of malignant cells. Plant isoprenoids, including beta-ionone and geraniol, have previously been shown to inhibit rodent mammary tumor development, and rodent and avian hepatic HMG-CoA reductase activity. We hypothesized that the putative anti-proliferative and cell cycle inhibitory effects of beta-ionone and geraniol on MCF-7 human breast cancer cells in culture are mediated by mevalonate depletion resulting from inhibition of HMG-CoA reductase activity. Flow cytometric analysis showed a G1 arrest in isoprenoid-treated MCF-7 cells, and also a G2/M arrest at higher concentrations of isoprenoids. These compounds minimally affected the growth of MCF-10F normal breast epithelial cells. Both beta-ionone and geraniol inhibited CDK 2 activity and dose-dependently decreased the expression of cyclins D1, E, and A, and CDK 2 and 4, without changing the expression of p21cip1 or p27kip1. Although both beta-ionone and geraniol also inhibited MCF-7 proliferation, only geraniol inhibited HMG-CoA reductase activity. While these effects were significantly correlated (r2=0.89, P <0.01), they were not causally related, since exogenous mevalonate did not restore growth in geraniol-inhibited cells. These findings indicate that mechanisms other than impaired mevalonate synthesis mediate the anti-proliferative and cell cycle regulatory effects of beta-ionone and geraniol in human breast cancer cells.
PMID: 15450939

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