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Biochemical and biophysical research communications v.494 no.3/4, 2017년, pp.477 - 483   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

A chemical screen identifies trifluoperazine as an inhibitor of glioblastoma growth

Pinheiro, Tiago (Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden ) ; Otrocka, Magdalena (Chemical Biology Consortium Sweden, Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden ) ; Seashore-Ludlow, Brinton (Chemical Biology Consortium Sweden, Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden ) ; Rraklli, Vilma (Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden ) ; Holmberg, Johan (Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden ) ; Forsberg-Nilsson, Karin (Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden ) ; Simon, András (Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden ) ; Kirkham, Matthew (Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden ) ;
  • 초록  

    Abstract 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 2HCl 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. Highlights Screening of GBM cells uncovers 45 active dopaminergic ligands and 8 were validated. Ligand selectivity suggests dopamine-mediated cell viability regulation in GBM. The DRD2 antagonist trifluoperazine inhibits cell viability and growth of GBM cells. DR expression profile of GBM cells alter the susceptibility to trifluoperazine.


  • 주제어

    Glioblastoma .   Trifluoperazine .   Dopamine .   Cancer .   Screening .   Cell lines.  

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