cytotoxicity of the urokinase-plasminogen activator inhibitor carbamimidothioic acid (4-boronophenyl) methyl ester hydrobromide (bc-11) on triple-negative mda-mb231 breast cancer cells
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2015
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Abstract
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: (i) 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 for the development of this class of compounds in the prevention and/or therapy of “aggressive” breast carcinoma.
| Reference Key |
longo2015moleculescytotoxicity
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| Authors | ;Alessandra Longo;Mariangela Librizzi;Irina S. Chuckowree;Christine B. Baltus;John Spencer;Claudio Luparello |
| Journal | Journal of ethnopharmacology |
| Year | 2015 |
| DOI |
10.3390/molecules20069879
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