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The microtubule targeting agent PBOX-15 inhibits integrin-mediated cell adhesion and induces apoptosis in acute lymphoblastic leukaemia cells.
MedLine Citation:
PMID:  23135704     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Joanne Lysaght; Navin K Verma; Elaina N Maginn; Jacqueline M Ryan; Giuseppe Campiani; Daniela M Zisterer; D Clive Williams; Paul V Browne; Mark P Lawler; Anthony M McElligott
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-06
Journal Detail:
Title:  International journal of oncology     Volume:  -     ISSN:  1791-2423     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Haematology, John Durkan Leukaemia Laboratories, Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland.
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