Palladium and platinum complexes of folic acid as new drug delivery systems for treatment of breast cancer cells

Abstract Cisplatin is administrated as an agent in treatment of various cancers by intercalation between DNA strands and inhibition of DNA replication. Among the various factors, two important reasons like inhibition of apoptosis by anti-apoptotic mechanisms and inability to distinguish normal cells from cancerous led us to synthesize two new complexes of platinum and palladium containing folic acid (FA). Following, the cytotoxic effects of complexes were studied using MTT assay in MCF-7 cells, then expression levels of Bak1, Bclx and Caspase-3 genes were elucidated by Real-time RT-PCR technique. Also, the behavior of complexes in the binding sites of folate receptor was described by molecular docking. All experiments have confirmed that presence of FA could improve cytotoxicity, apoptosis and cellular uptake of cisplatin in MCF-7 breast cancer cells. In addition, formation of 2,2′-bipyridine palladium(II) chelate with FA decreased the anti-apoptotic Bclx levels in comparison with cisplatin.