Iron(III)-salen complexes with less DNA cleavage activity exhibit more efficient apoptosis in MCF7 cells

• Published in: Organic & biomolecular chemistry Vol. 7; no. 5; pp. 926 - 932
• Main Authors: Ansari, Khairul I., Grant, James D., Woldemariam, Getachew A., Kasiri, Sahba, Mandal, Subhrangsu S.
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 01.01.2009
• Subjects: Apoptosis - drug effects; Cell Line, Tumor; Chelating Agents - pharmacology; Chemistry; Chemistry, Organic; DNA Cleavage - drug effects; Ethylenediamines - pharmacology; Female; Ferric Compounds - pharmacology; Humans; Physical Sciences; Science & Technology; CISPLATIN; RNA; SALEN COMPLEXES; HYDROLYSIS; ANTICANCER DRUGS; AGENTS; BINDING; CANCER; METAL-COMPLEXES; DAMAGE
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/b816858j

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.