char = I;code = 73
char = n;code = 110
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char = v;code = 118
char = i;code = 105
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char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
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char = ;code = 32
char = d;code = 100
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char = c;code = 99
char = h;code = 104
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char = o;code = 111
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char = c;code = 99
char = e;code = 101
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char = t;code = 116
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char = a;code = 97
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char = O;code = 79
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = .;code = 46
result sql = In vitro effects of dichloroacetate and CO2 on hypoxic HeLa cells.
In vitro effects of dichloroacetate and CO2 on hypoxic HeLa cells.
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = h;code = 104
char = y;code = 121
char = p;code = 112
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
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 = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = u;code = 117
char = m;code = 109
char = ;code = 32
char = p;code = 112
char = H;code = 72
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = w;code = 119
char = a;code = 97
char = r;code = 114
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 = 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 = a;code = 97
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = b;code = 98
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = n;code = 110
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 = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = D;code = 68
char = C;code = 67
char = A;code = 65
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 = h;code = 104
char = y;code = 121
char = p;code = 112
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = n;code = 110
char = u;code = 117
char = m;code = 109
char = b;code = 98
char = e;code = 101
char = r;code = 114
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 = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
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 = 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 = s;code = 115
char = ;code = 32
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = D;code = 68
char = C;code = 67
char = A;code = 65
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = l;code = 108
char = l;code = 108
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 = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = H;code = 72
char = .;code = 46
char = ;code = 32
char = I;code = 73
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 = h;code = 104
char = y;code = 121
char = p;code = 112
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = a;code = 97
char = -;code = 45
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
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = 1;code = 49
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = u;code = 117
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = ;code = 32
char = (;code = 40
char = H;code = 72
char = I;code = 73
char = F;code = 70
char = 1;code = 49
char = A;code = 65
char = );code = 41
char = ;code = 32
char = m;code = 109
char = R;code = 82
char = N;code = 78
char = A;code = 65
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 = i;code = 105
char = n;code = 110
char = ;code = 32
char = h;code = 104
char = y;code = 121
char = p;code = 112
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = H;code = 72
char = e;code = 101
char = L;code = 76
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 = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = i;code = 105
char = r;code = 114
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = D;code = 68
char = -;code = 45
char = g;code = 103
char = l;code = 108
char = u;code = 117
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = b;code = 98
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = g;code = 103
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = f;code = 102
char = i;code = 105
char = r;code = 114
char = m;code = 109
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 = r;code = 114
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = a;code = 97
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
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 = i;code = 105
char = n;code = 110
char = c;code = 99
char = u;code = 117
char = b;code = 98
char = a;code = 97
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 = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = C;code = 67
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
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 = h;code = 104
char = y;code = 121
char = p;code = 112
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
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 = i;code = 105
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = l;code = 108
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 = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = i;code = 105
char = r;code = 114
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 = o;code = 111
char = f;code = 102
char = ;code = 32
char = A;code = 65
char = T;code = 84
char = P;code = 80
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = c;code = 99
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 = c;code = 99
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = n;code = 110
char = g;code = 103
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = l;code = 108
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = r;code = 114
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 = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = n;code = 110
char = u;code = 117
char = m;code = 109
char = b;code = 98
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = y;code = 121
char = p;code = 112
char = e;code = 101
char = ;code = 32
char = 1;code = 49
char = ;code = 32
char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
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 = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = w;code = 119
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = h;code = 104
char = y;code = 121
char = p;code = 112
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
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 = 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 = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = h;code = 104
char = y;code = 121
char = p;code = 112
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = a;code = 97
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = D;code = 68
char = C;code = 67
char = A;code = 65
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 = 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 = c;code = 99
char = o;code = 111
char = u;code = 117
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 = h;code = 104
char = y;code = 121
char = p;code = 112
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = ,;code = 44
char = ;code = 32
char = D;code = 68
char = C;code = 67
char = A;code = 65
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
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = s;code = 115
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = a;code = 97
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = c;code = 99
char = e;code = 101
char = e;code = 101
char = d;code = 100
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = s;code = 115
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 = l;code = 108
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = D;code = 68
char = C;code = 67
char = A;code = 65
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 = D;code = 68
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = i;code = 105
char = t;code = 116
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 = i;code = 105
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = t;code = 116
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = h;code = 104
char = y;code = 121
char = p;code = 112
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = v;code = 118
char = i;code = 105
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
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result sql = HeLa and PANC-1 cells were exposed to conflicting signals promoting anaerobic or aerobic energy-generating processes and their viability, cell numbers and the ability of HeLa cells to form colonies were assessed. Under conventional aerobic cell culture with 5% CO(2), dichloroacetate (DCA), an inhibitor of the enzyme pyruvate dehydrogense kinase with subsequent stimulation of pyruvate dehydrogenase that redirects energy metabolism toward the Kreb cycle, reduced HeLa and PANC-1 cellular proliferation and viability. With nitrogen-induced hypoxia, the number of control cells and cells cultured with 12.5 mM DCA paradoxically was greater than that of normoxic controls under similar conditions. A higher medium pH of cells cultured under nitrogen contributed to these differences. In 96-well experiments, 95% nitrogen with 5% CO(2) reduced the numbers of hypoxic cells and medium pH toward that of the aerobic controls, with retention of the DCA-induced hypoxic compared to normoxic cell numbers. The media of these cells cultured with DCA still exhibited an increased pH. Increased hypoxia-inducible factor 1, alpha subunit (HIF1A) mRNA expression in hypoxic HeLa cells and their greater reliance on D-glucose for metabolic energy confirmed the reliability of the incubation conditions. Compared with normoxic cells, hypoxic cells initially increased their synthesis of ATP, but once proliferation ceased, this no longer closely correlated with cell numbers. Type 1 apoptosis, which was somewhat greater in hypoxic than normoxic cells, contributed to hypoxia and DCA-induced cell death. Colony counts of hypoxic, DCA-inhibited cells subsequently switched to normoxia exceeded those of similarly treated normoxic DCA cells. Despite inhibition in certain hypoxic environments of pyruvate dehydrogenase kinase by DCA and its contribution to increased cellular apoptosis and necrosis, hypoxic cells generally outnumbered normoxic control cells, as did hypoxic DCA-treated cells compared with comparable DCA-treated normoxic cells. Since in vivo hypoxic cells are considered a major factor contributing to therapeutic failure, and as DCA redirects energy metabolism toward the more energy efficient Kreb citric acid cycle, associated with increased medium (and inferred cellular) pH, similar circumstances in vivo could promote proliferation and survival of hypoxic cell clones with the potential for developing unwanted properties.

Publication: Anticancer Res. 2009 Nov ;29(11)::4579-88.
Publication Date: 2009 Nov
Study Author(s): Anderson, K M;Jajeh, J;Guinan, P;Rubenstein, M;
Institution: Hektoen Institute LLC, Chicago, IL, USA. [email protected]
Shortcut link to this study:
HeLa and PANC-1 cells were exposed to conflicting signals promoting anaerobic or aerobic energy-generating processes and their viability, cell numbers and the ability of HeLa cells to form colonies were assessed. Under conventional aerobic cell culture with 5% CO(2), dichloroacetate (DCA), an inhibitor of the enzyme pyruvate dehydrogense kinase with subsequent stimulation of pyruvate dehydrogenase that redirects energy metabolism toward the Kreb cycle, reduced HeLa and PANC-1 cellular proliferation and viability. With nitrogen-induced hypoxia, the number of control cells and cells cultured with 12.5 mM DCA paradoxically was greater than that of normoxic controls under similar conditions. A higher medium pH of cells cultured under nitrogen contributed to these differences. In 96-well experiments, 95% nitrogen with 5% CO(2) reduced the numbers of hypoxic cells and medium pH toward that of the aerobic controls, with retention of the DCA-induced hypoxic compared to normoxic cell numbers. The media of these cells cultured with DCA still exhibited an increased pH. Increased hypoxia-inducible factor 1, alpha subunit (HIF1A) mRNA expression in hypoxic HeLa cells and their greater reliance on D-glucose for metabolic energy confirmed the reliability of the incubation conditions. Compared with normoxic cells, hypoxic cells initially increased their synthesis of ATP, but once proliferation ceased, this no longer closely correlated with cell numbers. Type 1 apoptosis, which was somewhat greater in hypoxic than normoxic cells, contributed to hypoxia and DCA-induced cell death. Colony counts of hypoxic, DCA-inhibited cells subsequently switched to normoxia exceeded those of similarly treated normoxic DCA cells. Despite inhibition in certain hypoxic environments of pyruvate dehydrogenase kinase by DCA and its contribution to increased cellular apoptosis and necrosis, hypoxic cells generally outnumbered normoxic control cells, as did hypoxic DCA-treated cells compared with comparable DCA-treated normoxic cells. Since in vivo hypoxic cells are considered a major factor contributing to therapeutic failure, and as DCA redirects energy metabolism toward the more energy efficient Kreb citric acid cycle, associated with increased medium (and inferred cellular) pH, similar circumstances in vivo could promote proliferation and survival of hypoxic cell clones with the potential for developing unwanted properties.
PMID: 20032407

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