Supramolecular iron cylinder with unprecedented DNA binding is a potent cytostatic and apoptotic agent without exhibiting genotoxicity.
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.
Hotze
Anna C G
AC
School of Chemistry, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Hodges
Nikolas J
NJ
Hayden
Rachel E
RE
Sanchez-Cano
Carlos
C
Paines
Christopher
C
Male
Natalia
N
Tse
Man-Kit
MK
Bunce
Chris M
CM
Chipman
J Kevin
JK
Hannon
Michael J
MJ
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D054697:Cytostatic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D005296:Ferrous Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008928:Mitochondria / Q000187:drug effects; D008958:Models, Molecular; D009152:Mutagenicity Tests; D009369:Neoplasms / Q000628:therapy*
D054697:Cytostatic Agents; D005296:Ferrous Compounds; D004247:DNA; D002945:Cisplatin