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result sql = Role of zinc and iron chelation in apoptosis mediated by tachpyridine, an anti-cancer iron chelator.

Role of zinc and iron chelation in apoptosis mediated by tachpyridine, an anti-cancer iron chelator.

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char = t;code = 116
char = a;code = 97
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char = a;code = 97
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char = a;code = 97
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char = l;code = 108
char = u;code = 117
char = l;code = 108
char = a;code = 97
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char = l;code = 108
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char = e;code = 101
char = l;code = 108
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char = o;code = 111
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char = [;code = 91
char = F;code = 70
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char = t;code = 116
char = a;code = 97
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char = -;code = 45
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char = (;code = 40
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char = e;code = 101
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char = t;code = 116
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char = t;code = 116
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char = T;code = 84
char = a;code = 97
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char = h;code = 104
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char = t;code = 116
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char = n;code = 110
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = h;code = 104
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 = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
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 = 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 = h;code = 104
char = e;code = 101
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 = z;code = 122
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = y;code = 121
char = ;code = 32
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
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 = a;code = 97
char = c;code = 99
char = h;code = 104
char = p;code = 112
char = y;code = 121
char = r;code = 114
char = i;code = 105
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
result sql = Tachpyridine (N,N',N"-tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane; tachpyr) is a potent hexadentate iron chelator under preclinical investigation as a potential anti-cancer agent. Tachpyridine induces apoptosis in cultured cancer cells by triggering a mitochondrial pathway of cell death that is p53-independent. To explore the relationship between the chelation chemistry of tachpyridine and its biological activity, a sensitive and specific reversed-phase high-performance liquid chromatography (RP-HPLC) method was devised and used to measure tachpyr and its metal complexes in cells and tissue culture media. Major species identified in cells treated with tachpyr were tachpyr itself, [Zn(tachpyr)](2+), and iron coordinated to two partially oxidized species of tachpyridine, [Fe(tachpyr-ox-2)](2+), and [Fe(tachpyr-ox-4)](2+). The kinetics of intracellular accumulation of [Zn(tachpyr)](2+) and [Fe(tachpyr-ox-2)](2+) were markedly different: [Zn(tachpyr)](2+) rapidly reached plateau levels, whereas intracellular levels of [Fe(tachpyr-ox-2)](2+) and free tachpyr rose steadily. At the last timepoint measured, 9% of total cellular iron and 13% of total cellular zinc were bound by tachpyridine. Taken together, [Zn(tachpyr)](2+), [Fe(tachpyr-ox-2)](2+), and free tachpyr accounted for virtually all of the tachpyr added, indicating that iron and zinc are the principal metals targeted by tachpyridine in cells. Consistent with these findings, activation of the apoptotic caspases 9 and 3 was blocked in cells pre-treated with either iron or zinc. Pretreatment with either of these metals also completely protected cells from the cytotoxic effects of tachpyridine. These results demonstrate a link between metal depletion and chelator cytotoxicity, and suggest that intracellular chelation of zinc as well as iron may play a role in the cytotoxicity of tachpyridine.

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