Anti-proliferative impact of three Schiff base platinum (II) complexes against human breast cancer cell line

Treatment approaches for breast cancer (BC) are challenging in terms of tumor recurrence and drug resistance. We investigated the antitumor activity of three platinum (II) complexes bearing Schiff base ligands against breast cancer cells MCF-7. MCF-7 cells were treated with three platinum complexes and drug cytotoxicity was evaluated using an MTT assay. To quantify apoptosis and to confirm the mode of cell death, flowcytometry analysis using annexin V-FITC-PI kit and DNA fragmentation assay was used, respectively. The possible cytotoxic mechanism of action of these platinum compounds was also determined through mRNA expression analysis by the Real time PCR method. All complexes show a dose-dependent inhibitory effect on cell viability. flowcytometry analysis shows that the average percentage of apoptosis in 50 mu M concentration of all complexes is 23 +/- 3.5% and DNA fragmentation assay confirmed apoptosis. Treatment of cells with complexes significantly decreases mRNA expression of topoisomerase 1 and 2 and Bcl-2 as compared to untreated control cells. Also, our results show that both caspase 6 and 9 genes expression levels were induced at high dose (50 mu M) of complexes. Our findings indicate that three Schiff base platinum (II) complexes have potent antiproliferative effect against breast cancer cells and induce apoptosis via the mitochondrial pathway. Also, our data provide evidence for a possible role of Schiff base platinum complexes in inhibition of breast tumor progression through downregulation of HIF-1 alpha, topoisomerase 1 and 2 genes. These data support the idea that these complexes would be promising anti-breast cancer drugs.