Antiproliferative activity of selected non-steroidal anti-inflammatory agents: role of iron complexes

In this work the complexation of five NSAIDs with iron [Fe[3+]] was studied and the role of these iron complexes in reducing the proliferation of cancer cells was investigated. The stoichiometry and the formation constants of the complexes formed with different NSAIDs were calculated using the conductivity method. The metal-drug ratio for all drugs was 1:2 and their formation constant values were between 10[9] to 10[14]. The antiproliferative activity of the NSAIDs in their free and complex form was assessed using MCF-7 cells. After 72 hours incubation with the free drugs, mefenamic acid and diclofenac sodium showed the strongest antiproliferative effects with IC[50] of 70.54 +/- 15.29 microM and 108.38 +/- 11.28 microM, respectively. Indomethacin, naproxen and meloxicam had moderate to no effect at the concentrations tested. A linear correlation, with r= 0.876, between the formation constants of NSAlDs-Fe[3+] complexes and their cytotoxic effects was observed after 6 hours incubation. The ability of each drug to bind to DNA was examined together with the influence of ferric ions on the binding process. Drug-iron complexes were shown to bind to DNA, though with slightly different ratio. The results suggest that the complexes possess intrinsic cytotoxic effect