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char = t;code = 116
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char = n;code = 110
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char = f;code = 102
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char = p;code = 112
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char = s;code = 115
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char = e;code = 101
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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
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 = b;code = 98
char = y;code = 121
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = e;code = 101
char = n;code = 110
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = -;code = 45
char = c;code = 99
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char = u;code = 117
char = m;code = 109
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = n;code = 110
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char = 6;code = 54
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char = 7;code = 55
char = -;code = 45
char = d;code = 100
char = i;code = 105
char = o;code = 111
char = x;code = 120
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char = c;code = 99
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = c;code = 99
char = o;code = 111
char = p;code = 112
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = (;code = 40
char = I;code = 73
char = I;code = 73
char = );code = 41
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = x;code = 120
char = .;code = 46
result sql = An in vitro investigation of the induction of apoptosis and modulation of cell cycle events in human cancer cells by bisphenanthroline-coumarin-6,7-dioxacetatocopper(II) complex.
An in vitro investigation of the induction of apoptosis and modulation of cell cycle events in human cancer cells by bisphenanthroline-coumarin-6,7-dioxacetatocopper(II) complex.
char = T;code = 84
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char = a;code = 97
char = l;code = 108
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char = o;code = 111
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char = e;code = 101
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char = r;code = 114
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char = ;code = 32
char = n;code = 110
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char = n;code = 110
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char = p;code = 112
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = c;code = 99
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char = r;code = 114
char = e;code = 101
char = n;code = 110
char = a;code = 97
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char = K;code = 75
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char = 2;code = 50
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char = l;code = 108
char = s;code = 115
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char = a;code = 97
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char = p;code = 112
char = r;code = 114
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char = f;code = 102
char = i;code = 105
char = l;code = 108
char = e;code = 101
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char = s;code = 115
char = h;code = 104
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 = c;code = 99
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char = s;code = 115
char = p;code = 112
char = l;code = 108
char = a;code = 97
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 = ;code = 32
char = o;code = 111
char = b;code = 98
char = s;code = 115
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char = r;code = 114
char = v;code = 118
char = e;code = 101
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char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
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char = o;code = 111
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char = i;code = 105
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = a;code = 97
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char = i;code = 105
char = v;code = 118
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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
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char = p;code = 112
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char = a;code = 97
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char = e;code = 101
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char = t;code = 116
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char = b;code = 98
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char = c;code = 99
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char = n;code = 110
char = c;code = 99
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char = n;code = 110
char = t;code = 116
char = r;code = 114
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
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
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char = m;code = 109
char = e;code = 101
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char = d;code = 100
char = e;code = 101
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char = e;code = 101
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char = d;code = 100
char = a;code = 97
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char = t;code = 116
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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 = o;code = 111
char = u;code = 117
char = l;code = 108
char = d;code = 100
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char = b;code = 98
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = t;code = 116
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 = t;code = 116
char = h;code = 104
char = e;code = 101
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char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = x;code = 120
char = ,;code = 44
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
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char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = y;code = 121
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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 = 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
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char = p;code = 112
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = s;code = 115
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char = ;code = 32
char = i;code = 105
char = .;code = 46
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = 1;code = 49
char = ,;code = 44
char = 1;code = 49
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char = e;code = 101
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char = a;code = 97
char = n;code = 110
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char = h;code = 104
char = r;code = 114
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char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = c;code = 99
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char = u;code = 117
char = m;code = 109
char = a;code = 97
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char = i;code = 105
char = n;code = 110
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char = i;code = 105
char = g;code = 103
char = a;code = 97
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char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = o;code = 111
char = r;code = 114
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char = t;code = 116
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char = e;code = 101
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char = s;code = 115
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = l;code = 108
char = e;code = 101
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char = m;code = 109
char = e;code = 101
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char = a;code = 97
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = a;code = 97
char = l;code = 108
char = t;code = 116
char = .;code = 46
char = ;code = 32
char = F;code = 70
char = u;code = 117
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
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char = m;code = 109
char = p;code = 112
char = l;code = 108
char = e;code = 101
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char = w;code = 119
char = a;code = 97
char = s;code = 115
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char = s;code = 115
char = h;code = 104
char = o;code = 111
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char = n;code = 110
char = ;code = 32
char = t;code = 116
char = o;code = 111
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char = d;code = 100
char = e;code = 101
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 = ;code = 32
char = D;code = 68
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = s;code = 115
char = y;code = 121
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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 = 44
char = ;code = 32
char = b;code = 98
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char = t;code = 116
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char = d;code = 100
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char = d;code = 100
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char = t;code = 116
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char = t;code = 116
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char = t;code = 116
char = h;code = 104
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char = i;code = 105
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char = a;code = 97
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char = e;code = 101
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char = I;code = 73
char = C;code = 67
char = (;code = 40
char = 5;code = 53
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char = [;code = 91
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char = a;code = 97
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char = (;code = 40
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char = e;code = 101
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char = 2;code = 50
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char = ];code = 93
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char = o;code = 111
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char = t;code = 116
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char = b;code = 98
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char = a;code = 97
char = l;code = 108
char = m;code = 109
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char = s;code = 115
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char = x;code = 120
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char = a;code = 97
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char = ;code = 32
char = M;code = 77
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char = r;code = 114
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char = a;code = 97
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char = t;code = 116
char = h;code = 104
char = a;code = 97
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char = P;code = 80
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char = o;code = 111
char = t;code = 116
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char = p;code = 112
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char = i;code = 105
char = a;code = 97
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char = e;code = 101
char = d;code = 100
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char = t;code = 116
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char = r;code = 114
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char = s;code = 115
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char = s;code = 115
char = t;code = 116
char = a;code = 97
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char = (;code = 40
char = M;code = 77
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char = R;code = 82
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char = ;code = 32
char = w;code = 119
char = a;code = 97
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char = D;code = 68
char = N;code = 78
char = A;code = 65
char = ,;code = 44
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char = a;code = 97
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char = a;code = 97
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result sql = The central objective of the current study was to investigate the potential in vitro anti-proliferative properties of the parent ligand, coumarin-dioxy-acetic acid (cdoaH(2)), and its copper complex, copper-coumarin-dioxyacetic acetate-phenathroline ([Cu(cdoa)(phen)(2)]) using four human-derived model cell lines, two neoplastic and two non-neoplastic. In addition, selected mechanistic studies were carried out using one of the neoplastic-derived model cell lines, Hep-G2. Results obtained show that the complex, rather than the ligand, could alter the proliferation of both human neoplastic renal (A-498) and hepatic (Hep-G2) cells. Furthermore, hepatic non-neoplastic cells (Chang) appeared to be less sensitive. However, this effect was not mirrored in non-neoplastic renal (HK-2) cells, a profile shared with cisplatin. The observed anti-proliferative effect appeared to be concentration- and time-dependant, and could be attributed to the complex, rather than any of the component parts, i.e. 1,10-phenanthroline, the coumarin ligand, or the simple metal salt. Furthermore, the complex was shown to decrease DNA synthesis, but did not intercalate with it. Based on IC(50) values, [Cu(cdoa)(phen)(2)] was shown to be almost six times more potent than cisplatin. Moreover, there was no evidence to show that P-glycoprotein (P-gp)-mediated multi-drug resistance (MDR) was likely to play a role in decreasing the anti-proliferative activity of the complex. Cytological stains, analysis of genomic DNA, and biochemical assays [caspase-3 and -9 and cleaved poly(ADP-ribose)-polymerase protein], suggested that cell death could switch between apoptosis and necrosis, and this effect appeared to be concentration-dependent. Additionally, flow cytometric analysis showed that the complex functioned through an alteration in cell cycle progression. Taken together, [Cu(cdoa)(phen)(2)] has been shown to be a more potent anti-proliferative agent than either the ligand or cisplatin, and is capable of altering key biochemical events leading to the execution of apoptotic and/or necrotic cell death, suggesting that it is worthy of further investigation.

Publication: Chem. Biol. Interact. 2007 Jun 30 ;168(2)::143-58.
Publication Date: 2007 Jun 30
Study Author(s): Thati, Bhumika;Noble, Andy;Creaven, Bernadette S;Walsh, Maureen;Kavanagh, Kevin;Egan, Denise A;
Institution: Centre for Pharmaceutical Research & Development, Institute of Technology, Tallaght, Dublin 24, Ireland.
Shortcut link to this study:
The central objective of the current study was to investigate the potential in vitro anti-proliferative properties of the parent ligand, coumarin-dioxy-acetic acid (cdoaH(2)), and its copper complex, copper-coumarin-dioxyacetic acetate-phenathroline ([Cu(cdoa)(phen)(2)]) using four human-derived model cell lines, two neoplastic and two non-neoplastic. In addition, selected mechanistic studies were carried out using one of the neoplastic-derived model cell lines, Hep-G2. Results obtained show that the complex, rather than the ligand, could alter the proliferation of both human neoplastic renal (A-498) and hepatic (Hep-G2) cells. Furthermore, hepatic non-neoplastic cells (Chang) appeared to be less sensitive. However, this effect was not mirrored in non-neoplastic renal (HK-2) cells, a profile shared with cisplatin. The observed anti-proliferative effect appeared to be concentration- and time-dependant, and could be attributed to the complex, rather than any of the component parts, i.e. 1,10-phenanthroline, the coumarin ligand, or the simple metal salt. Furthermore, the complex was shown to decrease DNA synthesis, but did not intercalate with it. Based on IC(50) values, [Cu(cdoa)(phen)(2)] was shown to be almost six times more potent than cisplatin. Moreover, there was no evidence to show that P-glycoprotein (P-gp)-mediated multi-drug resistance (MDR) was likely to play a role in decreasing the anti-proliferative activity of the complex. Cytological stains, analysis of genomic DNA, and biochemical assays [caspase-3 and -9 and cleaved poly(ADP-ribose)-polymerase protein], suggested that cell death could switch between apoptosis and necrosis, and this effect appeared to be concentration-dependent. Additionally, flow cytometric analysis showed that the complex functioned through an alteration in cell cycle progression. Taken together, [Cu(cdoa)(phen)(2)] has been shown to be a more potent anti-proliferative agent than either the ligand or cisplatin, and is capable of altering key biochemical events leading to the execution of apoptotic and/or necrotic cell death, suggesting that it is worthy of further investigation.
PMID: 17512508

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