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

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 May 28;20(6):9879-89. doi: 10.3390/molecules20069879.
Alessandra Longo 1,  Mariangela Librizzi 2,  Irina S Chuckowree 3 4,  Christine B Baltus 4,  John Spencer 3 4,  Claudio Luparello 5
Affiliations

Affiliations

  • 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.
PMID: 26029857 DOI: 10.3390/molecules20069879
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.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z