The anti-helminthic niclosamide inhibits Wnt/Frizzled1 signaling

Biochemistry. 2009 Nov 3;48(43):10267-74. doi: 10.1021/bi9009677.


Wnt proteins bind to seven-transmembrane Frizzled receptors to mediate the important developmental, morphogenetic, and stem cell related tissue-regenerative effects of Wnt signaling. Dysregulated Wnt signaling is associated with many cancers. Currently, there are no drug candidates or even tool compounds that modulate Wnt-mediated receptor trafficking, and subsequent Wnt signaling. We examined libraries of FDA-approved drugs for their utility as Frizzled internalization modulators, employing a primary imaged-based GFP fluorescence assay that uses Frizzled1 endocytosis as the readout. We now report that the anti-helminthic niclosamide, a drug used for the treatment of tapeworm, promotes Frizzled1 endocytosis, downregulates Dishevelled-2 protein, and inhibits Wnt3A-stimulated beta-catenin stabilization and LEF/TCF reporter activity. Additionally, following niclosamide-mediated internalization, the Frizzled1 receptor colocalizes in vesicles containing transferrin and agonist-activated beta(2)-adrenergic receptor. Therefore, niclosamide may serve as a negative modulator of Wnt/Frizzled1 signaling by depleting upstream signaling molecules (i.e., Frizzled and Dishevelled) and moreover may provide a valuable means of studying the physiological consequences of Wnt signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antinematodal Agents / pharmacology
  • Cell Line
  • Cell Line, Tumor
  • Endocytosis / drug effects
  • Frizzled Receptors / metabolism*
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Microscopy, Confocal
  • Niclosamide / pharmacology*
  • Rats
  • Signal Transduction / drug effects*
  • Wnt Proteins / metabolism*
  • beta Catenin / metabolism


  • Antinematodal Agents
  • Frizzled Receptors
  • Wnt Proteins
  • beta Catenin
  • Green Fluorescent Proteins
  • Niclosamide