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

Alessandra Longo³  Mariangela Librizzi³  Irina S. Chuckowree²  Christine B. Baltus¹  John Spencer²  Claudio Luparello³ 

[1] School of Science at Medway, University of Greenwich, Chatham ME4 4TB, UK; E-Mail:;Department of Chemistry, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QJ, UK; E-Mails:;Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Edificio 16, Università di Palermo, Viale delle Scienze, 90128 Palermo, Italy; E-Mails:

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

DOI  :  10.3390/molecules20069879

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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