University of Sussex
Browse
Molecules_with_claudio_bc11.pdf (879.26 kB)

Cytotoxicity of the urokinase-plasminogen activator inhibitor carbamimidothioic acid (4-boronophenyl) methyl ester hydrobromide (BC-11) on triple-negative MDA-MB231 breast cancer cells

Download (879.26 kB)
journal contribution
posted on 2023-06-08, 20:55 authored by Alessandra Longo, Mariangela Librizzi, Irina Chuckowree, Christine B Baltus, John SpencerJohn Spencer, Claudio Luparello
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Molecules

ISSN

1420-3049

Publisher

MDPI

Issue

6

Volume

20

Page range

9879-9889

Department affiliated with

  • Chemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2015-05-29

First Open Access (FOA) Date

2015-05-29

First Compliant Deposit (FCD) Date

2015-05-29

Usage metrics

    University of Sussex (Publications)

    Categories

    No categories selected

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC