Evaluation of a Schiff base copper complex compound as potent anticancer molecule with multiple targets of action

Copper is a biologically relevant metal as it is associated with various biomolecules related to essential physiological activities. Anticancer compounds with copper as a metal center is hypothesized to be less toxic and more potent. In the present study we have tested the efficacy of a family of Schiff base copper complexes of which the best compound was [Cu(Pyimpy)Cl-2] where Pyimpy is a tridentate ligand containing two pyridine and one (mine nitrogen donor. [Cu(Pyimpy)Cl-2], represented as CuP1, was checked for its anticancer potential. The IC50 value of CuP1 was found to be 4.29 +/- 0.42, 6.34 +/- 0.58 and 5.32 +/- 0.38 mu M in MCF-7, PC3 and HEK 293 cells respectively. It was found to cause in vitro DNA fragmentation in comet assays and acridine orange staining of MCF 7 cells. CuP1 was further tested on rat breast tumor models and was found to inhibit tumor growth. It caused apoptosis within the tumor by the up regulation of caspase pathway and inhibition of the Akt, matrix metalloproteinase 9 and a-methyl acyl CoA racemase. Antioxidant enzymes which in general results in drug resistant condition in tumor tissues were significantly inhibited by this copper compound (P<0.05). Further, CuP1 did not show any prominent systemic toxicity. These results indicate that CuP1 can be a potential anticancer agent and further investigation will reveal more about its mode of action. (c) 2010 Elsevier B.V. All rights reserved.