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char = h;code = 104
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char = G;code = 71
char = R;code = 82
char = P;code = 80
char = 7;code = 55
char = 8;code = 56
char = ;code = 32
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char = e;code = 101
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char = n;code = 110
char = ;code = 32
char = 7;code = 55
char = 0;code = 48
char = .;code = 46
result sql = Synergistic promotion of breast cancer cells death by targeting molecular chaperone GRP78 and heat shock protein 70.
Synergistic promotion of breast cancer cells death by targeting molecular chaperone GRP78 and heat shock protein 70.
char = H;code = 72
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char = (;code = 40
char = H;code = 72
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char = s;code = 115
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char = i;code = 105
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char = s;code = 115
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char = s;code = 115
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char = T;code = 84
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char = H;code = 72
char = S;code = 83
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char = o;code = 111
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char = ;code = 32
char = H;code = 72
char = S;code = 83
char = P;code = 80
char = 7;code = 55
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char = (;code = 40
char = U;code = 85
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char = R;code = 82
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char = s;code = 115
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char = G;code = 71
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char = 7;code = 55
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char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
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 = y;code = 121
char = p;code = 112
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = U;code = 85
char = P;code = 80
char = R;code = 82
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = C;code = 67
char = H;code = 72
char = O;code = 79
char = P;code = 80
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 = 44
char = ;code = 32
char = e;code = 101
char = I;code = 73
char = F;code = 70
char = 2;code = 50
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 = J;code = 74
char = N;code = 78
char = K;code = 75
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 = 44
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = s;code = 115
char = p;code = 112
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = s;code = 115
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 = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = X;code = 88
char = B;code = 66
char = P;code = 80
char = -;code = 45
char = 1;code = 49
char = ;code = 32
char = s;code = 115
char = p;code = 112
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = b;code = 98
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
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 = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = -;code = 45
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = v;code = 118
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = G;code = 71
char = R;code = 82
char = P;code = 80
char = 7;code = 55
char = 8;code = 56
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = s;code = 115
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = z;code = 122
char = e;code = 101
char = s;code = 115
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 = t;code = 116
char = o;code = 111
char = ;code = 32
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = r;code = 114
char = c;code = 99
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = C;code = 67
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = n;code = 110
char = y;code = 121
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = v;code = 118
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = a;code = 97
char = y;code = 121
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = m;code = 109
char = o;code = 111
char = n;code = 110
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 = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
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 = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = a;code = 97
char = ;code = 32
char = (;code = 40
char = -;code = 45
char = );code = 41
char = -;code = 45
char = e;code = 101
char = p;code = 112
char = i;code = 105
char = g;code = 103
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = c;code = 99
char = h;code = 104
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = g;code = 103
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = E;code = 69
char = G;code = 71
char = C;code = 67
char = G;code = 71
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = A;code = 65
char = T;code = 84
char = P;code = 80
char = -;code = 45
char = b;code = 98
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 = ;code = 32
char = d;code = 100
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = G;code = 71
char = R;code = 82
char = P;code = 80
char = 7;code = 55
char = 8;code = 56
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
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 = f;code = 102
char = u;code = 117
char = n;code = 110
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = g;code = 103
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
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 = d;code = 100
char = ;code = 32
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = r;code = 114
char = c;code = 99
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = -;code = 45
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = h;code = 104
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 = s;code = 115
char = t;code = 116
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = a;code = 97
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 = H;code = 72
char = S;code = 83
char = P;code = 80
char = 7;code = 55
char = 0;code = 48
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = w;code = 119
char = n;code = 110
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 = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = d;code = 100
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = 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
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = U;code = 85
char = P;code = 80
char = R;code = 82
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = -;code = 45
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = v;code = 118
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = G;code = 71
char = R;code = 82
char = P;code = 80
char = 7;code = 55
char = 8;code = 56
char = ;code = 32
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
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = r;code = 114
char = c;code = 99
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = b;code = 98
char = r;code = 114
char = o;code = 111
char = g;code = 103
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 = G;code = 71
char = R;code = 82
char = P;code = 80
char = 7;code = 55
char = 8;code = 56
char = ;code = 32
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
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = r;code = 114
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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
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 = G;code = 71
char = R;code = 82
char = P;code = 80
char = 7;code = 55
char = 8;code = 56
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 = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = s;code = 115
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char = t;code = 116
char = h;code = 104
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 = i;code = 105
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = r;code = 114
char = c;code = 99
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = n;code = 110
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
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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 = c;code = 99
char = o;code = 111
char = m;code = 109
char = b;code = 98
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = s;code = 115
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 = o;code = 111
char = f;code = 102
char = ;code = 32
char = f;code = 102
char = l;code = 108
char = a;code = 97
char = v;code = 118
char = o;code = 111
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char = o;code = 111
char = i;code = 105
char = d;code = 100
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = p;code = 112
char = a;code = 97
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = p;code = 112
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = H;code = 72
char = S;code = 83
char = P;code = 80
char = 7;code = 55
char = 0;code = 48
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = G;code = 71
char = R;code = 82
char = P;code = 80
char = 7;code = 55
char = 8;code = 56
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = r;code = 114
char = c;code = 99
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
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result sql = Heat shock protein 70 (HSP70) is frequently overexpressed in a variety of human malignancies and protects cancer cells against apoptosis in response to various stresses. The bioflavonoid quercetin inhibits HSP70 expression and induces cancer cells apoptosis. In the present study, we have investigated the effects of HSP70 down-regulation on the unfolded protein response (UPR) and addressed a novel strategy to enhance the proapoptotic effect of quercetin by suppressing GRP78 induction simultaneously. Treatment of human breast cancer cells with quercetin down-regulates HSP70 expression, but up-regulates GRP78 expression in a dose-dependent manner. Down-regulation of HSP70 by small interfering RNA also leads to induction of GRP78. Moreover, our studies reveal that HSP70 knockdown or quercetin induces other typical components of the UPR, including CHOP expression, eIF2alpha and JNK phosphorylation, caspases activation and XBP-1 splicing. Abrogating the induction of pro-survival chaperone GRP78 by small interfering RNA sensitizes breast cancer cells to quercetin. Colony survival assays demonstrate that treatment of breast cancer cells with green tea (-)-epigallocatechin gallate (EGCG), which binds to the ATP-binding domain of GRP78 and blocks its protective function, synergistically promoted quercetin-induced cell death. These studies reveal that HSP70 down-regulation leads to the induction of UPR. The pro-survival GRP78 induction contributes to quercetin resistance. Abrogation of GRP78 induction or inhibition of GRP78 activity increases the effectiveness of quercetin. These findings indicate that combinational administration of flavonoids capable of suppressing HSP70 and GRP78 such as quercetin and EGCG might represent a novel approach for cancer therapy or chemoprevention.

Publication: J. Cell. Mol. Med. 2009 Nov-Dec ;13(11-12)::4540-50. :doi: 10.1111/j.1582-4934.2008.00575.x.
Publication Date: 2009 Nov-Dec
Study Author(s): Li, Minjing;Wang, Jiao;Jing, Jian;Hua, Hui;Luo, Ting;Xu, Li;Wang, Ranran;Liu, Dongbo;Jiang, Yangfu;
Institution: Division of Signal Transduction and Molecular Targeting Therapy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Shortcut link to this study:
Heat shock protein 70 (HSP70) is frequently overexpressed in a variety of human malignancies and protects cancer cells against apoptosis in response to various stresses. The bioflavonoid quercetin inhibits HSP70 expression and induces cancer cells apoptosis. In the present study, we have investigated the effects of HSP70 down-regulation on the unfolded protein response (UPR) and addressed a novel strategy to enhance the proapoptotic effect of quercetin by suppressing GRP78 induction simultaneously. Treatment of human breast cancer cells with quercetin down-regulates HSP70 expression, but up-regulates GRP78 expression in a dose-dependent manner. Down-regulation of HSP70 by small interfering RNA also leads to induction of GRP78. Moreover, our studies reveal that HSP70 knockdown or quercetin induces other typical components of the UPR, including CHOP expression, eIF2alpha and JNK phosphorylation, caspases activation and XBP-1 splicing. Abrogating the induction of pro-survival chaperone GRP78 by small interfering RNA sensitizes breast cancer cells to quercetin. Colony survival assays demonstrate that treatment of breast cancer cells with green tea (-)-epigallocatechin gallate (EGCG), which binds to the ATP-binding domain of GRP78 and blocks its protective function, synergistically promoted quercetin-induced cell death. These studies reveal that HSP70 down-regulation leads to the induction of UPR. The pro-survival GRP78 induction contributes to quercetin resistance. Abrogation of GRP78 induction or inhibition of GRP78 activity increases the effectiveness of quercetin. These findings indicate that combinational administration of flavonoids capable of suppressing HSP70 and GRP78 such as quercetin and EGCG might represent a novel approach for cancer therapy or chemoprevention.
PMID: 19017364

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