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Propofol-induced calcium signalling and actin reorganization within breast carcinoma cells

Published online by Cambridge University Press:  28 July 2005

V. Garib ,
K. Lang ,
B. Niggemann ,
K. S. Zänker ,
L. Brandt  and
T. Dittmar
V. Garib
Affiliation:
University of Witten/Herdecke, Institute of Immunology, Witten, Germany
K. Lang
Affiliation:
University of Witten/Herdecke, Institute of Immunology, Witten, Germany
B. Niggemann
Affiliation:
University of Witten/Herdecke, Institute of Immunology, Witten, Germany
K. S. Zänker
Affiliation:
University of Witten/Herdecke, Institute of Immunology, Witten, Germany
L. Brandt
Affiliation:
University of Witten/Herdecke, Institute of Anaesthesiology, Wuppertal, Germany
T. Dittmar
Affiliation:
University of Witten/Herdecke, Institute of Immunology, Witten, Germany
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Summary

Background and objective: MDA-MB-468 breast carcinoma cells respond to non-volatile anaesthetics such as propofol with an increased migration. Here we investigated the relationship between GABA-A receptor modulators, the mode of calcium oscillation and actin reorganization with regard to breast carcinoma cell migration. Methods: Expression of the GABA-A receptor was determined by Western blot analysis. Calcium-imaging experiments of individual MDA-MB-468 cells as well as visualization of the F-actin distribution were performed by confocal laser scanning microscopy. Cell migration was investigated in a three-dimensional collagen matrix by time-lapse video microscopy. The GABA agonist propofol was used in a final concentration of 6 μg mL−1. GABA-A receptor antagonist bicuculline (50 μmol) and selective L-type calcium channel blocker verapamil (5 μmol) were used to modulate the propofol effects. Results: A functional GABA-A receptor is expressed by MDA-MB-468 cells. Activation with propofol resulted in sustained increased intracellular calcium concentrations concomitant with actin reorganization and induction of migration in MDA-MB-468 cells. These propofol effects were completely blocked by verapamil. Spontaneous migration of MDA-MB-468 cells (64.4 ± 7.0%) was significantly increased by propofol to 85.0 ± 5.0%. MDA-MB-468 cells co-treated with propofol and verapamil showed a migratory activity of 63.0 ± 2.0% indicating that verapamil blocked the propofol effect. Similar results were achieved with the GABA-A receptor inhibitor bicuculline (control: 56.3 ± 8.5%; propofol: 80.5 ± 7.1%; propofol + bicuculline: 52.5 ± 8.6%). Conclusion: Activation of GABA-A receptor by propofol correlated with an increased migration of MDA-MB-468 breast carcinoma cells, mediated by calcium influx via L-type calcium channels and reorganization of the actin cytoskeleton.

Keywords

ANAESTHETICS, INTRAVENOUS, propofolBREAST NEOPLASMS, breast cancerCALCIUM SIGNALLING, calcium oscillationF-ACTIN, actin reorganization
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 22 , Issue 8 , August 2005 , pp. 609 - 615
Copyright
© 2005 European Society of Anaesthesiology

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