SASPject PT1.2

Mucin 1 (MUC1) is overexpressed in various cancer cells especially in breast cancer cells. There are known research works on the use of anti-MUC1 antibody with docetaxel in ovarian cancer, but there are no data about combined therapy platinum compounds with anti-MUC1 in breast cancer. The aim of the study was to evaluate the antiproliferative properties of a new dinuclear platinum(II) complex (Pt12) used with anti-MUC1 in human breast cancer cells. The dinuclear platinum(II) complex (Pt12) has been synthesized, and its cytotoxicity with anti-MUC1 has been tested in both MCF-7 and MDA-MB-231 breast cancer cells. In this study, the effects of Pt12 with anti-MUC1 on collagen and DNA biosynthesis in human breast cancer cells were compared to those evoked by cisplatin and cisplatin with anti-MUC1. The mechanism of action of Pt12 with anti-MUC1 was studied employing flow cytometry assessment of annexin V binding assay. It was found that Pt12 with anti-MUC1 was more active inhibitor of DNA and collagen synthesis as well more cytotoxic agent than Pt12 alone and cisplatin with anti-MUC1. Cytotoxicity of Pt12 with anti-MUC1 against breast cancer cells is due to apoptotic cell death as well as necrotic cell death. These results indicate that the use of Pt12 with anti-MUC1 may constitute a novel strategy in the chemotherapy of breast cancer tumors.

Mucin 1 (MUC1) is a high molecular weight transmembrane glycoprotein, that is overexpressed in >90% of breast cancers. It serves a crucial role in anti-apoptosis and tumor progression. MUC1 interacts with proteins in the extracellular matrix, at the cell membrane, in the cytoplasm and in the nucleus. The aim of the present study was to investigate the mechanism of anticancer action induced by novel berenil complex of platinum(II) (Pt12) together with a monoclonal antibody against MUC1 in breast cancer MCF-7 cells. The effect of combined treatment on the concentration of selected markers of apoptosis including proapoptotic B-cell lymphoma 2 associated X protein (Bax), caspase-8, cytochrome c and caspase-9, as well as selected proteins involved in intracellular signal transduction pathways including p53, phosphoinositide 3-kinase and phosphorylated protein kinase B (p-Akt) were analyzed. The results of the present study demonstrated that combined treatment may be a promising strategy in anticancer treatment and represents an alternative to monotherapy. All compounds used alone (Pt12, cisplatin and the anti-MUC1 antibody) increased the concentration of proapoptotic Bax, cytochrome c and caspase-9 in comparison with control, thus suggesting that they activated the mitochondrial apoptotic pathway. Pt12 alone significantly increased the concentration of caspase-8, which is responsible for the initiation of the extrinsic apoptotic pathway. However, the strongest effect was observed following Pt12 (20 µM) treatment combined with the anti-MUC1 antibody (10 µg/ml). These two compounds together strongly induced apoptosis in MCF-7 breast cancer cells via the external and internal apoptotic pathways. It was also demonstrated that combined treatment based on Pt12 and the anti-MUC1 antibody significantly reduced p-Akt concentration.