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result sql = Discovery of chrysoeriol, a PI3K-AKT-mTOR pathway inhibitor with potent antitumor activity against human multiple myeloma cells in vitro.
Discovery of chrysoeriol, a PI3K-AKT-mTOR pathway inhibitor with potent antitumor activity against human multiple myeloma cells in vitro.
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char = c;code = 99
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = n;code = 110
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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 = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = r;code = 114
char = y;code = 121
char = s;code = 115
char = o;code = 111
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = o;code = 111
char = p;code = 112
char = t;code = 116
char = e;code = 101
char = d;code = 100
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 = l;code = 108
char = t;code = 116
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 = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = -;code = 45
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 = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = C;code = 67
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = B;code = 66
char = 1;code = 49
char = ,;code = 44
char = ;code = 32
char = C;code = 67
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 = 44
char = ;code = 32
char = p;code = 112
char = 2;code = 50
char = 1;code = 49
char = );code = 41
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = P;code = 80
char = I;code = 73
char = 3;code = 51
char = K;code = 75
char = -;code = 45
char = A;code = 65
char = K;code = 75
char = T;code = 84
char = -;code = 45
char = m;code = 109
char = T;code = 84
char = O;code = 79
char = R;code = 82
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 = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = e;code = 101
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 = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = W;code = 87
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = y;code = 121
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = 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 = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = i;code = 105
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = y;code = 121
char = e;code = 101
char = l;code = 108
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = 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 = b;code = 98
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = r;code = 114
char = y;code = 121
char = s;code = 115
char = o;code = 111
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = o;code = 111
char = l;code = 108
char = ,;code = 44
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 = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = i;code = 105
char = n;code = 110
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 = i;code = 105
char = n;code = 110
char = ;code = 32
char = G;code = 71
char = (;code = 40
char = 2;code = 50
char = );code = 41
char = /;code = 47
char = M;code = 77
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 = 46
char = ;code = 32
char = C;code = 67
char = h;code = 104
char = r;code = 114
char = y;code = 121
char = s;code = 115
char = o;code = 111
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = u;code = 117
char = l;code = 108
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
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 = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = -;code = 45
char = A;code = 65
char = K;code = 75
char = T;code = 84
char = ;code = 32
char = (;code = 40
char = s;code = 115
char = 4;code = 52
char = 7;code = 55
char = 3;code = 51
char = );code = 41
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = -;code = 45
char = 4;code = 52
char = e;code = 101
char = B;code = 66
char = P;code = 80
char = 1;code = 49
char = ;code = 32
char = (;code = 40
char = t;code = 116
char = 3;code = 51
char = 7;code = 55
char = /;code = 47
char = 4;code = 52
char = 6;code = 54
char = );code = 41
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = a;code = 97
char = n;code = 110
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = C;code = 67
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = B;code = 66
char = 1;code = 49
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = 2;code = 50
char = 1;code = 49
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = 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 = 46
char = ;code = 32
char = S;code = 83
char = i;code = 105
char = m;code = 109
char = i;code = 105
char = l;code = 108
char = a;code = 97
char = r;code = 114
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 = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = b;code = 98
char = s;code = 115
char = e;code = 101
char = r;code = 114
char = v;code = 118
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 = 80
char = B;code = 66
char = M;code = 77
char = N;code = 78
char = C;code = 67
char = s;code = 115
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = n;code = 110
char = o;code = 111
char = r;code = 114
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = t;code = 116
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = d;code = 100
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = r;code = 114
char = y;code = 121
char = s;code = 115
char = o;code = 111
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = P;code = 80
char = I;code = 73
char = 3;code = 51
char = K;code = 75
char = -;code = 45
char = A;code = 65
char = K;code = 75
char = T;code = 84
char = -;code = 45
char = m;code = 109
char = T;code = 84
char = O;code = 79
char = R;code = 82
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 = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = t;code = 116
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = 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 = 32
char = o;code = 111
char = f;code = 102
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 = m;code = 109
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = i;code = 105
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = y;code = 121
char = e;code = 101
char = l;code = 108
char = o;code = 111
char = m;code = 109
char = a;code = 97
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 = 44
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = d;code = 100
char = n;code = 110
char = ';code = 39
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 = ;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 = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = P;code = 80
char = B;code = 66
char = M;code = 77
char = N;code = 78
char = C;code = 67
char = s;code = 115
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = n;code = 110
char = o;code = 111
char = r;code = 114
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = t;code = 116
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = t;code = 116
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
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 = 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 = ;code = 32
char = v;code = 118
char = i;code = 105
char = a;code = 97
char = ;code = 32
char = t;code = 116
char = h;code = 104
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 = 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 = 80
char = I;code = 73
char = 3;code = 51
char = K;code = 75
char = -;code = 45
char = A;code = 65
char = K;code = 75
char = T;code = 84
char = -;code = 45
char = m;code = 109
char = T;code = 84
char = O;code = 79
char = R;code = 82
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 = 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 = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
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result sql = This study was designed to determine the impact of chrysoeriol on proliferation and cell cycle progression in the human multiple myeloma cell lines RPMI 8226 and KM3, and its related molecular mechanisms. Chryseoriol was identified by using the phosphorylated AKT-specific cytoblot high throughput assay. CCK-8 assay was employed to examine the growth inhibition rate and IC(50) (48 h) in peripheral blood mononuclear cells (PBMNCs), RPMI 8226 and KM3 cells treated with chrysoeriol at various concentrations. Cells were labeled with 5-6-carboxyfluorescein diacetate succinimidyl ester (CFSE), and the proliferation dynamics was detected by flow cytometry and analyzed with ModFit software. The cell cycles of RPMI 8226 and KM3 cells were measured by flow cytometry when the IC(50) concentration of chrysoeriol was adopted. The alterations in cell-cycle related proteins (Cyclin B1, Cyclin D1, p21) and proteins in PI3K-AKT-mTOR pathway were determined by Western blot analysis. The results showed the proliferation of multiple myeloma cells was significantly inhibited by chrysoeriol, resulting in cell cycle arrest in G(2)/M phase. Chrysoeriol could significantly reduce the expression of p-AKT (s473) and p-4eBP1 (t37/46) protein, meanwhile enhanced Cyclin B1 and p21 protein expression. Similar effects were not observed in PBMNCs from normal donors. It was concluded that chrysoeriol was a selective PI3K-AKT-mTOR pathway inhibitor. It restrained the proliferation of human multiple myeloma cells, but didn't affect proliferation of PBMNCs from normal donors. It might exhibit the cell cycle regulatory effect via the inhibition of PI3K-AKT-mTOR signal pathway.

Publication: J. Huazhong Univ. Sci. Technol. Med. Sci. 2010 Dec ;30(6)::734-40. :doi: 10.1007/s11596-010-0649-4.
Publication Date: 2010 Dec
Study Author(s): Yang, Yang;Zhou, Xiaoxi;Xiao, Min;Hong, Zhenya;Gong, Quan;Jiang, Lijun;Zhou, Jianfeng;
Institution: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. [email protected]
Shortcut link to this study:
This study was designed to determine the impact of chrysoeriol on proliferation and cell cycle progression in the human multiple myeloma cell lines RPMI 8226 and KM3, and its related molecular mechanisms. Chryseoriol was identified by using the phosphorylated AKT-specific cytoblot high throughput assay. CCK-8 assay was employed to examine the growth inhibition rate and IC(50) (48 h) in peripheral blood mononuclear cells (PBMNCs), RPMI 8226 and KM3 cells treated with chrysoeriol at various concentrations. Cells were labeled with 5-6-carboxyfluorescein diacetate succinimidyl ester (CFSE), and the proliferation dynamics was detected by flow cytometry and analyzed with ModFit software. The cell cycles of RPMI 8226 and KM3 cells were measured by flow cytometry when the IC(50) concentration of chrysoeriol was adopted. The alterations in cell-cycle related proteins (Cyclin B1, Cyclin D1, p21) and proteins in PI3K-AKT-mTOR pathway were determined by Western blot analysis. The results showed the proliferation of multiple myeloma cells was significantly inhibited by chrysoeriol, resulting in cell cycle arrest in G(2)/M phase. Chrysoeriol could significantly reduce the expression of p-AKT (s473) and p-4eBP1 (t37/46) protein, meanwhile enhanced Cyclin B1 and p21 protein expression. Similar effects were not observed in PBMNCs from normal donors. It was concluded that chrysoeriol was a selective PI3K-AKT-mTOR pathway inhibitor. It restrained the proliferation of human multiple myeloma cells, but didn't affect proliferation of PBMNCs from normal donors. It might exhibit the cell cycle regulatory effect via the inhibition of PI3K-AKT-mTOR signal pathway.
PMID: 21181363

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