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Molecules 2015, 20(6), 9879-9889; doi:10.3390/molecules20069879

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

1
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Edificio 16, Università di Palermo, Viale delle Scienze, 90128 Palermo, Italy
2
Department of Chemistry, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QJ, UK
3
School of Science at Medway, University of Greenwich, Chatham ME4 4TB, UK
*
Author to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 4 March 2015 / Revised: 19 May 2015 / Accepted: 25 May 2015 / Published: 28 May 2015
(This article belongs to the Special Issue Recent Advances in Boron Chemistry)
View Full-Text   |   Download PDF [884 KB, uploaded 28 May 2015]   |  

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. View Full-Text
Keywords: boronic acid; BC-11; plasminogen activator inhibitor; breast cancer; cytotoxicity; MDA-MB231 cells boronic acid; BC-11; plasminogen activator inhibitor; breast cancer; cytotoxicity; MDA-MB231 cells
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Longo, A.; Librizzi, M.; Chuckowree, I.S.; Baltus, C.B.; Spencer, J.; Luparello, C. Cytotoxicity of the Urokinase-Plasminogen Activator Inhibitor Carbamimidothioic Acid (4-Boronophenyl) Methyl Ester Hydrobromide (BC-11) on Triple-Negative MDA-MB231 Breast Cancer Cells. Molecules 2015, 20, 9879-9889.

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