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The Microtubule Targeting Agent PBOX-15 Inhibits Integrin-Mediated Cell Adhesion and Induces Apoptosis in Acute Lymphoblastic Leukaemia Cells

The Microtubule Targeting Agent PBOX-15 Inhibits Integrin-Mediated Cell Adhesion and Induces Apoptosis in Acute Lymphoblastic Leukaemia Cells

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

Int J Oncol. 2013 Jan;42(1):239-46.

PMID: 23135704

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP354759107	PBOX-15		354759-10-7	Price

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