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Molecules. 2015 May 28;20(6):9879-89. 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.

Author information

1
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Edificio 16, Università di Palermo, Viale delle Scienze, 90128 Palermo, Italy. alessandra4682@hotmail.it.
2
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Edificio 16, Università di Palermo, Viale delle Scienze, 90128 Palermo, Italy. merylib@alice.it.
3
Department of Chemistry, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QJ, UK. christine.baltus@univ-tours.fr.
4
School of Science at Medway, University of Greenwich, Chatham ME4 4TB, UK. christine.baltus@univ-tours.fr.
5
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Edificio 16, Università di Palermo, Viale delle Scienze, 90128 Palermo, Italy. claudio.luparello@unipa.it.

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.

KEYWORDS:

BC-11; MDA-MB231 cells; boronic acid; breast cancer; cytotoxicity; plasminogen activator inhibitor

PMID:
26029857
PMCID:
PMC6272237
DOI:
10.3390/molecules20069879
[Indexed for MEDLINE]
Free PMC Article

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