Monoclonal anti-MUC1 antibody with novel octahydropyrazino[2,1-a:5,4-a′]diisoquinoline derivative as a potential multi-targeted strategy in MCF-7 breast cancer cells

The aim of the present study was to examine the multi-targeted potential of a monoclonal antibody against mucin-1 (MUC1) and novel octahydropyrazin[2,1-a:5,4-a ']diisoquinoline derivative (OM-86II) in estrogen receptor-positive MCF-7 human breast cancer cells. The cell viability was measured by an MTT assay. The analyses of cell cycle and disruption of mitochondrial membrane potential were performed by flow cytometry. Fluorescent microscopy and flow cytometry were used to demonstrate the effect of the compounds on apoptosis. ELISA was conducted to check the concentrations of proteins involved in multiple intracellular signaling pathways, responsible for the promotion of tumor growth and breast cancer progression, namely matrix metalloproteinase (MMP)-2, matrix MMP-9, tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2), soluble intercellular adhesion molecule 1 (sICAM1) and mTOR. The combination therapy based on anti-MUC1 antibody and novel OM-86II inhibited the proliferation of MCF-7 breast cancer cells. Its inhibitory effects were associated with the induction of cell cycle arrest and apoptosis. It was demonstrated that anti-MUC1 antibody with OM-86II decreased the concentrations of MMP-2, MMP-9, sICAM1 and mTOR. In addition, the combined therapy exhibited anti-inflammatory activity, which was demonstrated by a decrease in TNF-alpha and COX-2 concentrations. The present data provided evidence that the combination of anti-MUC1 antibody with novel OM-86II represents a multi-targeted strategy in MCF-7 breast cancer treatment.