Effects of Rhenium(I)-diselenoether and of its Diselenide Ligand on the Production of Cathepsins B and S by MDA-MB231 Breast Malignant Cells.

BACKGROUND/AIM: Rhenium(I)-diselenoether (Re-diSe) is a drug under development for the treatment of metastatic cancers, with selective inhibitory effects on MDA-MB231 cancer cells compared to normal HEK-293 cells, and with greater effects than its diselenide (di-Se) ligand. Rhenium (Re) compounds inhibit cathepsins, which are important proteolytic enzymes in cancer. This study investigated the effects of Re-diSe and di-Se on the production of cathepsins B and S in MDA-MB231 malignant and HEK-293 normal cells and their inhibitory effects following treatment with different doses for 72 h. MATERIALS AND METHODS: Elisa tests were used to assay the amount of cathepsins B and S in the medium of cultures. RESULTS: Re-diSe, but not diSe affected the viability of malignant cells and the expression of cathepsins B and S. CONCLUSION: To the best of our knowledge, this is the first demonstration that Re-diSe may decrease the production of cathepsins B and S in cancer cells at doses as low as 10 µM.

A New Model Applied for Evaluating a Rhenium-diselenium Drug: Breast Cancer Cells Stimulated by Cytokines Induced from Polynuclear Cells by LPS.

BACKGROUND/AIM: New anticancer drugs are usually tested on cancer cells in culture in a standard medium. We stimulated immune polynuclear cells by lipopolysaccharides to obtain an enriched medium (EM) containing inflammatory cytokines more closely reflecting the tumor microenvironment and tested a rhenium-diselenium (Re-diSe) drug in this new model. Concentrations of cytokines were compared with a control medium (CM). MATERIALS AND METHODS: Human-derived breast cancer cells were grown in culture either in CM or EM with or without Re-diSe. Assays of tumor necrosis factor alpha (TNFα), interleukin 6 (IL6), intereukin 1 beta (IL1ß), transforming growth factor-beta (TGFß), insulin growth factor 1 (IGF1) and vascular epidermal growth factor A (VEGFA) were performed by enzyme-linked immunosorbent assays. The production of reactive oxygen species (ROS) was determined by 2,7-dichlorofluorescein test. The cell growth was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tests. RESULTS: Concentrations of TNFα, IL6 and Il1ß were observed to be significantly higher in EM than in CM. There was no difference for TGFß, IGF1 and VEGFA. The cells were sensitive to Re-diSe, with reduced concentrations of TGFß, IGF1, VEGFA and ROS, but the half-maximal inhibitory concentration was significantly higher in EM than in CM. CONCLUSION: The efficacy of the Re-diSe drug was confirmed in this model of aggressive cancer.