Iron(III)-salen complexes with less DNA cleavage activity exhibit more efficient apoptosis in MCF7 cells.
To understand the relationship between DNA damage potential and biochemical activities, we synthesized nine different Fe(III)-salen derivatives with varying substituents, and analyzed their in vitro DNA cleavage properties and biochemical effects on cultured human cells. Our results demonstrated that Fe(III)-salen complexes affect cell viability, induce nuclear fragmentation, and activate caspases and apoptosis in cultured human cells. The nature and the position of the substituents in the Fe(III)-salen complexes play critical roles in determining their apoptotic efficiencies. Most importantly, our results demonstrated that the in vitro DNA cleavage activities of Fe(III)-salen complexes are not essential for their apoptotic activities in human cells. Instead, the lesser their DNA cleavage activity the greater is their apoptotic efficiency.
Ansari
Khairul I
KI
Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, Texas 76019, USA.
Grant
James D
JD
Woldemariam
Getachew A
GA
Kasiri
Sahba
S
Mandal
Subhrangsu S
SS
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000494:pharmacology*; D053837:DNA Cleavage / Q000187:drug effects*; D005029:Ethylenediamines / Q000494:pharmacology*; D005260:Female; D005290:Ferric Compounds / Q000494:pharmacology*; D006801:Humans
D002614:Chelating Agents; D005029:Ethylenediamines; D005290:Ferric Compounds; C011452:disalicylaldehyde ethylenediamine