Analytical Cellular Pathology

Analytical Cellular Pathology / 2012 / Article

Open Access

Volume 35 |Article ID 351674 | 18 pages | https://doi.org/10.3233/ACP-2012-0055

Targeting Focal Adhesion Assembly by Ethoxyfagaronine Prevents Lymphoblastic Cell Adhesion to Fibronectin

Received28 Jul 2011
Accepted06 Feb 2012

Abstract

Background: Leukemic cell adhesion to proteins of the bone marrow microenvironment provides signals which control morphology, motility and cell survival. We described herein the ability of ethoxyfagaronine (etxfag), a soluble synthetic derivative of fagaronine, to prevent leukemic cell adhesion to fibronectin peptide (FN/V).Methods: Phosphorylation of fak and pyk2 were evaluated by immunoblotting. Labelled proteins were localized by confocal microscopy. PI 3-kinase activity was evaluated by in vitro kinase assay.Results: Subtoxic concentration of etxfag reduced L1210 cell adhesion to FN/V dependently of β1 integrin engagement. Etxfag impaired FN-dependent formation of β1 clustering without modifying β1 expression at the cell membrane. This was accompanied by a decrease of focal adhesion number, a diminution of fak and pyk2 phosphorylation at Tyr-576, Tyr-861 and Tyr-579, respectively leading to their dissociations from β1 integrin and inhibition of PI 3-kinase activity. Etxfag also induced a cell retraction accompanied by a redistribution of phosphorylated fak and pyk2 in the perinuclear region and lipid raft relocalization.Conclusion: Through its anti-adhesive potential, etxfag, combined with conventional cytotoxic drugs could be potentially designed as a new anti-leukemic drug.

Copyright © 2012 Hindawi Publishing Corporation and the authors. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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