Mechanism of anticancer action of novel berenil complex of platinum(II) combined with anti-MUC1 in MCF-7 breast cancer cells
- Agnieszka Gornowicz
- Anna Bielawska
- Wojciech Szymanowski
- Halina Gabryel‑Porowska
- Robert Czarnomysy
- Krzysztof Bielawski
Published online on: December 14, 2017
Copyright: © Gornowicz et al.
This is an open access article distributed under the terms of Creative Commons Attribution License.
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.