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Phenobarbital inhibits calpain activity and expression in mouse hepatoma cells

  • Nicola Groll , Ferdinand Kollotzek , Jens Goepfert , Thomas O. Joos , Michael Schwarz and Albert Braeuning EMAIL logo
Published/Copyright: September 2, 2015

Abstract

The antiepileptic drug phenobarbital (PB) exerts hepatic effects related to cell proliferation and tumorigenesis which are closely linked to the Wnt/β-catenin signaling pathway. This pathway is, amongst others, regulated by calpain proteases. We now identified PB as an inhibitor of Wnt/β-catenin signaling in mouse hepatoma cells. Further analyses revealed that PB inhibits calpain activity, an effect which is at least in parts mediated by a transcriptional regulation of calpain mRNA levels and which is furthermore independent of the constitutive androstane receptor, the known mediator of most effects of PB in liver cells.


Corresponding author: Albert Braeuning, Department of Toxicology, University of Tübingen, Wilhelmstr. 56, D-72074 Tübingen, Germany; and Federal Institute for Risk Assessment, Department of Food Safety, Max-Dohrn-Str. 8-10, D-10589 Berlin, Germany, e-mail:

Acknowledgments

The authors acknowledge expert technical assistance by Silvia Vetter.

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Received: 2015-8-4
Accepted: 2015-8-31
Published Online: 2015-9-2
Published in Print: 2016-1-1

©2016 by De Gruyter

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