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A chemical screen identifies trifluoperazine as an inhibitor of glioblastoma growth
Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden..
Karolinska Inst, Dept Med Biochem & Biophys, Sci Life Lab, Chem Biol Consortium Sweden, Stockholm, Sweden..
Karolinska Inst, Dept Med Biochem & Biophys, Sci Life Lab, Chem Biol Consortium Sweden, Stockholm, Sweden..
Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden.;Karolinska Inst, Ludwig Inst Canc Res, Stockholm, Sweden..
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2017 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 494, no 3-4, p. 477-483Article in journal (Refereed) Published
Abstract [en]

Glioblastoma (GBM) is regarded as the most common malignant brain tumor but treatment options are limited. Thus, there is an unmet clinical need for compounds and corresponding targets that could inhibit GBM growth. We screened a library of 80 dopaminergic ligands with the aim of identifying compounds capable of inhibiting GBM cell line proliferation and survival. Out of 45 active compounds, 8 were further validated. We found that the dopamine receptor D2 antagonist trifluoperazine 2HC1 inhibits growth and proliferation of GBM cells in a dose dependent manner. Trifluoperazine's inhibition of GBM cells is cell line dependent and correlates with variations in dopamine receptor expression profile. We conclude that components of the dopamine receptor signaling pathways are potential targets for pharmacological interventions of GBM growth. (C) 2017 Elsevier Inc. All rights reserved.

Place, publisher, year, edition, pages
ACADEMIC PRESS INC ELSEVIER SCIENCE , 2017. Vol. 494, no 3-4, p. 477-483
Keywords [en]
Glioblastoma, Trifluoperazine, Dopamine, Cancer, Screening, Cell lines
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-343553DOI: 10.1016/j.bbrc.2017.10.106ISI: 000416393300008PubMedID: 29066348OAI: oai:DiVA.org:uu-343553DiVA, id: diva2:1187260
Available from: 2018-03-02 Created: 2018-03-02 Last updated: 2018-03-02Bibliographically approved

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