char = A;code = 65
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = n;code = 110
char = ;code = 32
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char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = s;code = 115
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char = d;code = 100
char = o;code = 111
char = x;code = 120
char = o;code = 111
char = r;code = 114
char = u;code = 117
char = b;code = 98
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = ;code = 32
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char = e;code = 101
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char = i;code = 105
char = s;code = 115
char = t;code = 116
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char = n;code = 110
char = c;code = 99
char = e;code = 101
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
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char = ;code = 32
char = c;code = 99
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char = l;code = 108
char = o;code = 111
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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 = v;code = 118
char = i;code = 105
char = a;code = 97
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = c;code = 99
char = i;code = 105
char = u;code = 117
char = m;code = 109
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 = H;code = 72
char = I;code = 73
char = F;code = 70
char = -;code = 45
char = 1;code = 49
char = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = P;code = 80
char = -;code = 45
char = g;code = 103
char = l;code = 108
char = y;code = 121
char = c;code = 99
char = o;code = 111
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 = o;code = 111
char = v;code = 118
char = e;code = 101
char = r;code = 114
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
result sql = Artemisinin induces doxorubicin resistance in human colon cancer cells via calcium-dependent activation of HIF-1alpha and P-glycoprotein overexpression.

Artemisinin induces doxorubicin resistance in human colon cancer cells via calcium-dependent activation of HIF-1alpha and P-glycoprotein overexpression.

char = <;code = 60
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char = R;code = 82
char = O;code = 79
char = U;code = 85
char = N;code = 78
char = D;code = 68
char = ;code = 32
char = A;code = 65
char = N;code = 78
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char = P;code = 80
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char = <;code = 60
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char = i;code = 105
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char = i;code = 105
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char = g;code = 103
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char = o;code = 111
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char = o;code = 111
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char = f;code = 102
char = e;code = 101
char = c;code = 99
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char = s;code = 115
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char = c;code = 99
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char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
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 = b;code = 98
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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
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char = h;code = 104
char = e;code = 101
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char = t;code = 116
char = r;code = 114
char = a;code = 97
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char = s;code = 115
char = c;code = 99
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char = p;code = 112
char = t;code = 116
char = i;code = 105
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char = f;code = 102
char = a;code = 97
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char = o;code = 111
char = r;code = 114
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char = n;code = 110
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char = c;code = 99
char = l;code = 108
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char = a;code = 97
char = r;code = 114
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = c;code = 99
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char = o;code = 111
char = r;code = 114
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char = k;code = 107
char = a;code = 97
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char = p;code = 112
char = a;code = 97
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char = B;code = 66
char = ;code = 32
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char = d;code = 100
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char = a;code = 97
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char = p;code = 112
char = l;code = 108
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char = s;code = 115
char = m;code = 109
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char = c;code = 99
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char = e;code = 101
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char = d;code = 100
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char = l;code = 108
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char = s;code = 115
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char = i;code = 105
char = c;code = 99
char = ;code = 32
char = r;code = 114
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char = t;code = 116
char = i;code = 105
char = c;code = 99
char = u;code = 117
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char = u;code = 117
char = m;code = 109
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char = C;code = 67
char = a;code = 97
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char = +;code = 43
char = +;code = 43
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char = -;code = 45
char = A;code = 65
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char = a;code = 97
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char = e;code = 101
char = ;code = 32
char = (;code = 40
char = S;code = 83
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char = R;code = 82
char = C;code = 67
char = A;code = 65
char = );code = 41
char = ;code = 32
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char = S;code = 83
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char = R;code = 82
char = C;code = 67
char = A;code = 65
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char = ;code = 32
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char = g;code = 103
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char = c;code = 99
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char = e;code = 101
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char = g;code = 103
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char = a;code = 97
char = c;code = 99
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char = l;code = 108
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = C;code = 67
char = a;code = 97
char = (;code = 40
char = +;code = 43
char = +;code = 43
char = );code = 41
char = ;code = 32
char = (;code = 40
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char = C;code = 67
char = a;code = 97
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char = +;code = 43
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char = );code = 41
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char = (;code = 40
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char = );code = 41
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char = ;code = 32
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char = e;code = 101
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char = e;code = 101
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char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
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char = ];code = 93
char = (;code = 40
char = i;code = 105
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char = e;code = 101
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char = s;code = 115
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char = ;code = 32
char = P;code = 80
char = g;code = 103
char = p;code = 112
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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
char = i;code = 105
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char = ,;code = 44
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char = d;code = 100
char = o;code = 111
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char = o;code = 111
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char = u;code = 117
char = b;code = 98
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = ;code = 32
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 = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
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char = i;code = 105
char = c;code = 99
char = i;code = 105
char = t;code = 116
char = y;code = 121
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char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = y;code = 121
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char = o;code = 111
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char = i;code = 105
char = a;code = 97
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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 = i;code = 105
char = b;code = 98
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char = e;code = 101
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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 = 44
char = ;code = 32
char = H;code = 72
char = I;code = 73
char = F;code = 70
char = -;code = 45
char = 1;code = 49
char = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
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char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = K;code = 75
char = E;code = 69
char = Y;code = 89
char = ;code = 32
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = U;code = 85
char = L;code = 76
char = T;code = 84
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = A;code = 65
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = o;code = 111
char = l;code = 108
char = i;code = 105
char = d;code = 100
char = e;code = 101
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char = ;code = 32
char = l;code = 108
char = i;code = 105
char = k;code = 107
char = e;code = 101
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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 = p;code = 112
char = e;code = 101
char = c;code = 99
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = S;code = 83
char = E;code = 69
char = R;code = 82
char = C;code = 67
char = A;code = 65
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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 = s;code = 115
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char = t;code = 116
char = h;code = 104
char = a;code = 97
char = p;code = 112
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = a;code = 97
char = r;code = 114
char = g;code = 103
char = i;code = 105
char = n;code = 110
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 = o;code = 111
char = p;code = 112
char = i;code = 105
char = a;code = 97
char = z;code = 122
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = c;code = 99
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char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
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 = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = S;code = 83
char = E;code = 69
char = R;code = 82
char = C;code = 67
char = A;code = 65
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = o;code = 111
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
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 = c;code = 99
char = a;code = 97
char = l;code = 108
char = c;code = 99
char = i;code = 105
char = u;code = 117
char = m;code = 109
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char = c;code = 99
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = e;code = 101
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char = t;code = 116
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 = (;code = 40
char = [;code = 91
char = C;code = 67
char = a;code = 97
char = (;code = 40
char = +;code = 43
char = +;code = 43
char = );code = 41
char = ];code = 93
char = (;code = 40
char = i;code = 105
char = );code = 41
char = );code = 41
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = P;code = 80
char = g;code = 103
char = p;code = 112
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
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
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = x;code = 120
char = o;code = 111
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char = u;code = 117
char = b;code = 98
char = i;code = 105
char = c;code = 99
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char = n;code = 110
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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 = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = c;code = 99
char = y;code = 121
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char = o;code = 111
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char = i;code = 105
char = c;code = 99
char = i;code = 105
char = t;code = 116
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char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
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char = i;code = 105
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char = a;code = 97
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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 = C;code = 67
char = a;code = 97
char = (;code = 40
char = +;code = 43
char = +;code = 43
char = );code = 41
char = ;code = 32
char = c;code = 99
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char = e;code = 101
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = 1;code = 49
char = ,;code = 44
char = 2;code = 50
char = -;code = 45
char = b;code = 98
char = i;code = 105
char = s;code = 115
char = (;code = 40
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char = a;code = 97
char = m;code = 109
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char = n;code = 110
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = e;code = 101
char = n;code = 110
char = o;code = 111
char = x;code = 120
char = y;code = 121
char = );code = 41
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = e;code = 101
char = -;code = 45
char = N;code = 78
char = ,;code = 44
char = N;code = 78
char = ,;code = 44
char = N;code = 78
char = ';code = 39
char = ,;code = 44
char = N;code = 78
char = ';code = 39
char = -;code = 45
char = t;code = 116
char = e;code = 101
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = a;code = 97
char = c;code = 99
char = e;code = 101
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char = i;code = 105
char = c;code = 99
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char = a;code = 97
char = c;code = 99
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char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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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
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 = a;code = 97
char = l;code = 108
char = m;code = 109
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char = d;code = 100
char = u;code = 117
char = l;code = 108
char = i;code = 105
char = n;code = 110
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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
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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 = I;code = 73
char = I;code = 73
char = ;code = 32
char = (;code = 40
char = C;code = 67
char = a;code = 97
char = M;code = 77
char = K;code = 75
char = I;code = 73
char = I;code = 73
char = );code = 41
char = ;code = 32
char = K;code = 75
char = N;code = 78
char = 9;code = 57
char = 3;code = 51
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
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 = 46
char = ;code = 32
char = C;code = 67
char = a;code = 97
char = M;code = 77
char = K;code = 75
char = I;code = 73
char = I;code = 73
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = k;code = 107
char = n;code = 110
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 = p;code = 112
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = p;code = 112
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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 = y;code = 121
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 = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = a;code = 97
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char = v;code = 118
char = a;code = 97
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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 = H;code = 72
char = I;code = 73
char = F;code = 70
char = -;code = 45
char = 1;code = 49
char = a;code = 97
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char = p;code = 112
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char = a;code = 97
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char = w;code = 119
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char = i;code = 105
char = c;code = 99
char = h;code = 104
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char = m;code = 109
char = a;code = 97
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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
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char = P;code = 80
char = g;code = 103
char = p;code = 112
char = .;code = 46
char = ;code = 32
char = I;code = 73
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char = H;code = 72
char = T;code = 84
char = 2;code = 50
char = 9;code = 57
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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 = 44
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = s;code = 115
char = i;code = 105
char = n;code = 110
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char = n;code = 110
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = p;code = 112
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 = o;code = 111
char = l;code = 108
char = i;code = 105
char = d;code = 100
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
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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 = p;code = 112
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char = o;code = 111
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char = p;code = 112
char = h;code = 104
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = H;code = 72
char = I;code = 73
char = F;code = 70
char = -;code = 45
char = 1;code = 49
char = a;code = 97
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char = p;code = 112
char = h;code = 104
char = a;code = 97
char = ,;code = 44
char = ;code = 32
char = w;code = 119
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char = i;code = 105
char = c;code = 99
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char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
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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
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = K;code = 75
char = N;code = 78
char = 9;code = 57
char = 3;code = 51
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = S;code = 83
char = ;code = 32
char = A;code = 65
char = N;code = 78
char = D;code = 68
char = ;code = 32
char = I;code = 73
char = M;code = 77
char = P;code = 80
char = L;code = 76
char = I;code = 73
char = C;code = 67
char = A;code = 65
char = T;code = 84
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = O;code = 79
char = u;code = 117
char = r;code = 114
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = g;code = 103
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = s;code = 115
char = i;code = 105
char = n;code = 110
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result sql = BACKGROUND AND PURPOSE : Artemisinin is an antimalarial drug exerting pleiotropic effects, such as the inhibition of the transcription factor nuclear factor-kappa B and of the sarcoplasmic/endoplasmic reticulum Ca(++)-ATPase (SERCA) of P. falciparum. As the sesquiterpene lactone thapsigargin, a known inhibitor of mammalian SERCA, enhances the expression of P-glycoprotein (Pgp) by increasing the intracellular Ca(++) ([Ca(++)](i)) level, we investigated whether artemisinin and its structural homologue parthenolide could inhibit SERCA in human colon carcinoma HT29 cells and induce a resistance to doxorubicin.

EXPERIMENTAL APPROACH : HT29 cells were incubated with artemisinin or parthenolide and assessed for SERCA activity, [Ca(++)](i) levels, Pgp expression, doxorubicin accumulation and toxicity, and translocation of the hypoxia-inducible factor, HIF-1alpha.

KEY RESULTS : Artemisinin and parthenolide, like the specific SERCA inhibitors thapsigargin and cyclopiazonic acid, reduced the activity of SERCA. They also increased intracellular calcium concentration ([Ca(++)](i)) and Pgp expression and decreased doxorubicin accumulation and cytotoxicity. The intracellular Ca(++) chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, and the inhibitor of calmodulin-dependent kinase II (CaMKII) KN93 prevented these effects. CaMKII is known to promote the phosphorylation and the activation of HIF-1alpha, which may induce Pgp. In HT29 cells, artemisinin and parthenolide induced the phosphorylation of HIF-1alpha, which was inhibited by KN93.

CONCLUSIONS AND IMPLICATIONS : Our results suggest that artemisinin and parthenolide may act as SERCA inhibitors and, like other SERCA inhibitors, induce resistance to doxorubicin in human colon cancer cells, via the CaMKII-dependent activation of HIF-1alpha and the induction of Pgp.

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