The microtubule targeting agent PBOX-15 inhibits integrin-mediated cell adhesion and induces apoptosis in acute lymphoblastic leukaemia cells
| Autor: | Mark Lawler, J Ryan, Paul Browne, Daniela M. Zisterer, D. Clive Williams, Navin Kumar Verma, Joanne Lysaght, Anthony M. McElligott, Giuseppe Campiani, Elaina N. Maginn |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Integrins
Cancer Research Cell type Cell cycle checkpoint Blotting Western Cell Integrin Fluorescent Antibody Technique Apoptosis Biology Microtubules Cell Movement Cell Adhesion Tumor Cells Cultured medicine Humans Pyrroles Cell adhesion Cell Proliferation Cell growth Cell Cycle Checkpoints Precursor Cell Lymphoblastic Leukemia-Lymphoma Cell cycle Flow Cytometry Cell biology Oxazepines medicine.anatomical_structure Oncology biology.protein |
| Popis: | Although recent decades have seen an improved cure rate for newly diagnosed paediatric acute lymphoplastic leukaemia (ALL), the treatment options for adult ALL, T-cell ALL (T-ALL) and relapsed disease remain poor. We have developed a novel series of pyrrolo-1,5-benzoxazepine (PBOX) compounds and established their anticancer efficacy in a variety of human tumour cell types. Here, we demonstrate that PBOX-15 inhibits cell growth, and induces G2/M cell cycle arrest and apoptosis in both T-ALL and B-cell ALL (B-ALL) cells. In addition, prior to PBOX-15-induced apoptosis, PBOX-15 decreases ALL cell adhesion, spreading and migration. Concurrently, PBOX-15 differentially down-regulates β1-, β2- and α4-integrin expression in ALL cells and significantly decreases integrin-mediated cell attachment. PBOX-15 interferes with the lateral mobility and clustering of integrins in both B-ALL and T-ALL cells. These data suggest that PBOX-15 is not only effective in inducing apoptosis in ALL cells, but also has the potential to disrupt integrin-mediated adhesion of malignant lymphocytes, which represents a novel avenue for regulating leukaemic cell homing and migration. |
| Databáze: | OpenAIRE |
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