TY - JOUR
T1 - Supramolecular iron cylinder with unprecedented DNA binding is a potent cytostatic and apoptotic agent without exhibiting genotoxicity.
AU - Hotze, AC
AU - Hodges, Nikolas
AU - Hayden, Rachel
AU - Sanchez-Cano, C
AU - Paines, C
AU - Male, N
AU - Tse, MK
AU - Bunce, Christopher
AU - Chipman, James
AU - Hannon, Michael
PY - 2008/12/22
Y1 - 2008/12/22
N2 - The supramolecular iron cylinder, [Fe(2)L(3)]Cl(4) (L = C(25)H(20)N(4)), shows unprecedented DNA binding in vitro, inducing intramolecular DNA coiling and also targeting Y-shaped DNA junctions. We investigated its effects on proliferation and survival in both tumor and normal cell lines. Iron cylinder reduced mitochondrial activity of cultures with potency similar to cisplatin, inhibited the cell cycle, and increased cell death by apoptosis. Associated with this, we observed a lowering of the association of propidium iodide with cellular DNA consistent with an observed competitive displacement of PI from naked DNA by cylinders. Importantly, and in contrast to existing anticancer drugs such as cisplatin, the iron cylinder [Fe(2)L(3)](4+) was not genotoxic. In summary, the design of metal complexes such as [Fe(2)L(3)](4+) with potential anticancer properties in the absence of genotoxicity may represent a significant step toward therapeutic advancement.
AB - The supramolecular iron cylinder, [Fe(2)L(3)]Cl(4) (L = C(25)H(20)N(4)), shows unprecedented DNA binding in vitro, inducing intramolecular DNA coiling and also targeting Y-shaped DNA junctions. We investigated its effects on proliferation and survival in both tumor and normal cell lines. Iron cylinder reduced mitochondrial activity of cultures with potency similar to cisplatin, inhibited the cell cycle, and increased cell death by apoptosis. Associated with this, we observed a lowering of the association of propidium iodide with cellular DNA consistent with an observed competitive displacement of PI from naked DNA by cylinders. Importantly, and in contrast to existing anticancer drugs such as cisplatin, the iron cylinder [Fe(2)L(3)](4+) was not genotoxic. In summary, the design of metal complexes such as [Fe(2)L(3)](4+) with potential anticancer properties in the absence of genotoxicity may represent a significant step toward therapeutic advancement.
U2 - 10.1016/j.chembiol.2008.10.016
DO - 10.1016/j.chembiol.2008.10.016
M3 - Article
C2 - 19101470
VL - 15
SP - 1258
EP - 1267
JO - Chemistry & Biology
JF - Chemistry & Biology
IS - 12
ER -