Antihelminth compound niclosamide downregulates Wnt signaling and elicits antitumor responses in tumors with activating APC mutations

Cancer Res. 2011 Jun 15;71(12):4172-82. doi: 10.1158/0008-5472.CAN-10-3978. Epub 2011 Apr 29.


Wnt/β-catenin pathway activation caused by adenomatous polyposis coli (APC) mutations occurs in approximately 80% of sporadic colorectal cancers (CRC). The antihelminth compound niclosamide downregulates components of the Wnt pathway, specifically Dishevelled-2 (Dvl2) expression, resulting in diminished downstream β-catenin signaling. In this study, we determined whether niclosamide could inhibit the Wnt/β-catenin pathway in human CRCs and whether its inhibition might elicit antitumor effects in the presence of APC mutations. We found that niclosamide inhibited Wnt/β-catenin pathway activation, downregulated Dvl2, decreased downstream β-catenin signaling, and exerted antiproliferative effects in human colon cancer cell lines and CRC cells isolated by surgical resection of metastatic disease, regardless of mutations in APC. In contrast, inhibition of NF-κB or mTOR did not exert similar antiproliferative effects in these CRC model systems. In mice implanted with human CRC xenografts, orally administered niclosamide was well tolerated, achieved plasma and tumor levels associated with biologic activity, and led to tumor control. Our findings support clinical explorations to reposition niclosamide for the treatment of CRC.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / analysis
  • Animals
  • Anthelmintics / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Dishevelled Proteins
  • Fibroblasts / drug effects
  • Genes, APC*
  • Humans
  • Mice
  • Mice, SCID
  • Mutation*
  • NF-kappa B / antagonists & inhibitors
  • Niclosamide / pharmacokinetics
  • Niclosamide / pharmacology*
  • Organoplatinum Compounds / pharmacology
  • Oxaliplatin
  • Phosphoproteins / analysis
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • Wnt Proteins / antagonists & inhibitors*
  • beta Catenin / analysis


  • Adaptor Proteins, Signal Transducing
  • Anthelmintics
  • Antineoplastic Agents
  • DVL2 protein, human
  • Dishevelled Proteins
  • Dvl2 protein, mouse
  • NF-kappa B
  • Organoplatinum Compounds
  • Phosphoproteins
  • Wnt Proteins
  • beta Catenin
  • Oxaliplatin
  • Niclosamide
  • TOR Serine-Threonine Kinases