Spiperone enhances intracellular calcium level and inhibits the Wnt signaling pathway.

BMC Pharmacology
Desheng Lu, Dennis A Carson

Abstract

Wnt signaling affects fundamental development pathways by regulating cell proliferation and differentiation. Aberrant activation of Wnt/beta-catenin signaling promotes the development of several cancers and is an attractive target for chemopreventive and chemotherapeutic agents. In order to identify the novel antagonists for the Wnt/beta-catenin pathway, we employed a cell-based Wnt reporter system (TOPflash) to screen a library of 960 known drugs. We identified spiperone, a psychotropic drug, as a novel Wnt inhibitor, which specifically blocks canonical Wnt signaling prior to the activation of beta-catenin. The Wnt inhibitory function of spiperone is not associated with its dopamine-, serotonin- and sigma-receptor antagonist properties. Instead, spiperone increases intracellular calcium levels in a similar manner to thapsigargin, that also impedes Wnt signal transduction. Inhibition of protein kinase C had no effect on spiperone-mediated antagonism of Wnt signaling. Spiperone is a calcium regulator. It inhibits Wnt signaling by enhancing intracellular calcium levels.

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Citations

Jan 13, 2012·Inflammatory Bowel Diseases·Manuel Luis Rodríguez-PerálvarezFederico Gómez-Camacho
Jul 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Desheng LuDennis A Carson
Jun 28, 2014·European Journal of Pharmacology·J Kyle BrunerMin Li
May 31, 2011·Canadian Journal of Physiology and Pharmacology·Yun WangHuai-Liang Wang
Dec 22, 2009·Scandinavian Journal of Clinical and Laboratory Investigation·Lars H Breimer, Dimitri P Mikhailidis
Sep 23, 2010·Assay and Drug Development Technologies·Christa HahmannThomas Schroeter
Apr 20, 2019·The Journal of Pharmacology and Experimental Therapeutics·Jillian S WeissenriederRaymond J Hohl
Jan 23, 2019·Frontiers in Cell and Developmental Biology·Khosrow S HouschyarBjörn Behr
Mar 7, 2017·Frontiers in Pharmacology·Karen S PoksayVarghese John
Jul 25, 2018·Proceedings of the National Academy of Sciences of the United States of America·Zijie SuDesheng Lu
Oct 13, 2018·The Science of the Total Environment·Jing TangZhiLiang Ji
Oct 23, 2020·Bioinformatics and Biology Insights·Deepak MavRichard S Paules
Jul 6, 2018·ACS Central Science·Xiaoli HuangDaniel Strand

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Methods Mentioned

BETA
transfection
transfections
flow cytometry

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