title: Cytotoxicity of the Urokinase-Plasminogen Activator Inhibitor Carbamimidothioic Acid (4-Boronophenyl) Methyl Ester Hydrobromide (BC-11) on Triple-Negative MDA-MB231 Breast Cancer Cells.
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.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Edificio 16, Università di Palermo, Viale delle Scienze, 90128 Palermo, Italy. alessandra4682@hotmail.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Longo
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Edificio 16, Università di Palermo, Viale delle Scienze, 90128 Palermo, Italy. merylib@alice.it.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Librizzi
authors.affiliation: Department of Chemistry, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QJ, UK. christine.baltus@univ-tours.fr.|School of Science at Medway, University of Greenwich, Chatham ME4 4TB, UK. christine.baltus@univ-tours.fr.
authors.forename: Irina S
authors.initials: IS
authors.lastname: Chuckowree
authors.affiliation: School of Science at Medway, University of Greenwich, Chatham ME4 4TB, UK. christine.baltus@univ-tours.fr.
authors.forename: Christine B
authors.initials: CB
authors.lastname: Baltus
authors.affiliation: Department of Chemistry, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QJ, UK. christine.baltus@univ-tours.fr.|School of Science at Medway, University of Greenwich, Chatham ME4 4TB, UK. christine.baltus@univ-tours.fr.
authors.forename: John
authors.initials: J
authors.lastname: Spencer
authors.affiliation: 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.
authors.forename: Claudio
authors.initials: C
authors.lastname: Luparello
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001897:Boronic Acids / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D042361:Mammary Glands, Human / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D015849:Plasminogen Inactivators / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D015849:Plasminogen Inactivators; D011799:Quinazolines; D017382:Reactive Oxygen Species; C512478:EGFR protein, human; D066246:ErbB Receptors; D014568:Urokinase-Type Plasminogen Activator; C088860:4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline
keywords: BC-11; MDA-MB231 cells; boronic acid; breast cancer; cytotoxicity; plasminogen activator inhibitor