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ToxSci Advance Access published online on November 21, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl167
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received August 23, 2006
Accepted November 7, 2006

In Vitro Toxicology

Azaspiracid-1 Alters the E-Cadherin Pool in Epithelial Cells

Giuseppe Ronzitti 1, Philipp Hess 2, Nils Rehmann 2, and Gian Paolo Rossini 1 *

1 Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, Via Campi 287, I-41100 Modena, Italy
2 Biotoxin Chemistry, Marine Environment and Food Safety Servics, Marine Institute, Rinville, Oranmore, County Galway, Ireland

* To whom correspondence should be addressed.
Gian Paolo Rossini, E-mail: rossini.gianpaolo{at}unimore.it


  Abstract

Azaspiracids cause severe damages in the epithelium of several organs. In this study we have investigated the effects of azaspiracid-1 (AZA-1) on two epithelial cell lines. Nanomolar concentrations of AZA-1 reduced MCF-7 cell proliferation and impaired cell-cell adhesion. AZA-1 altered the cellular pool of the adhesion molecule E-cadherin by inducing a dose- and time-dependent accumulation of an E-cadherin fragment (ECRA100), with an EC50 of 0.47 nM. The immunological characterization of ECRA100 revealed that it consists of an E-cadherin molecule lacking the intracellular domain, and these data showed that the effect induced by AZA-1 in MCF-7 cells is undistinguishable from that induced by yessotoxin in the same experimental system. A comparison of toxin effects in MCF-7 and Caco 2 cells confirmed that the effects induced by AZA-1 and yessotoxin are undistinguishable in these cells. Treatment of fibroblasts with AZA-1 did not affect the cellular pool of N-cadherin, showing that the toxin effect is cadherin-specific. A comparison of the effects induced by AZA-1, yessotoxin and okadaic acid on F-actin and E-cadherin in MCF-7 and Caco 2 cells showed that 1 nM AZA-1 did not cause significant changes in F-actin and that accumulation of ECRA100 did not correlate with decreased levels of F-actin under our experimental conditions. Matching our results with those available in literature, we notice that, when molecular effects induced by AZA-1 and yessotoxin have been studied in the same in vitro systems, experimental data show they are undistinguishable in terms of sensitive cellular parameters, effective doses, and kinetics of responses in several cell lines. The possibility that azaspiracids and yessotoxins might share their molecular mechanism(s) of action in defined biological settings should be considered.

Keywords: Azaspiracid; Yessotoxin; E-cadherin; N-cadherin; Epithelial cells; Okadaic acid.
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