Cytotoxicity of the Urokinase-Plasminogen Activator Inhibitor Carbamimidothioic Acid (4-Boronophenyl) Methyl Ester Hydrobromide (BC-11) on Triple-Negative MDA-MB231 Breast Cancer Cells

Alessandra Longo, Mariangela Librizzi, Irina Chuckowree, Christine Baltus, John Spencer, Claudio Luparello
2015 Molecules  
BC-11 is an easily synthesized simple thiouronium-substituted phenylboronic acid, which has been shown to be cytotoxic on triple negative MDA-MB231 breast cancer cells by inducing a perturbation of cell cycle when administered at a concentration equal to its ED50 at 72 h (117 μM). Exposure of cells to BC-11, either pre-absorbed with a soluble preparation of the N-terminal fragment of urokinase-plasminogen activator (uPa), or in co-treatment with two different EGFR inhibitors, indicated that:
more » ... BC-11 acts via binding to the N-terminus of the enzyme where uPa-and EGF receptor-recognizing sites are present, thereby abrogating the growth-sustaining effect resulting from receptor binding; and (ii) the co-presence of the EGFR inhibitor PD153035 potentiates BC-11's cytotoxicity. Exposure of cells to a higher concentration of BC-11 corresponding to its ED75 at 72 h (250 μM) caused additional impairment of mitochondrial activity, the production of reactive oxygen species and promotion of apoptosis. Therefore, BC-11 treatment appears to show potential OPEN ACCESS Molecules 2015, 20 9880 for the development of this class of compounds in the prevention and/or therapy of "aggressive" breast carcinoma.
doi:10.3390/molecules20069879 pmid:26029857 fatcat:ftqcwneprfgk5mhz7ze2ezsyey