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Analytical Cellular Pathology
Volume 35 (2012), Issue 4, Pages 267-284

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

F. Ouchani,1 J. Devy,1 A. Rusciani,1 J. J. Helesbeux,2 S. Salesse,1 I. Letinois,1 D. Gras-Billart,1 L. Duca,1 O. Duval,2 L. Martiny,1 and E. Charpentier1

1Université de Reims Champagne Ardenne, CNRS 6237 MEDyC, Laboratoire SiRMa, IFR 53 Interactions Cellules-Microenvironnement, Reims, France
2Université d’Angers, SONAS, UFR Sciences Pharmaceutiques et Ingénierie de la Santé, Angers, France

Received 28 July 2011; Accepted 6 February 2012

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.


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.