Possible repurposing of pyrvinium pamoate for the treatment of mesothelioma: A pre-clinical assessment

J Cell Physiol. 2018 Sep;233(9):7391-7401. doi: 10.1002/jcp.26579. Epub 2018 Apr 16.

Abstract

Malignant mesothelioma (MM) is a very aggressive asbestos-related cancer, whose incidence is increasing worldwide. Unfortunately, no effective therapies are currently available and the prognosis is extremely poor. Recently, the anti-helminthic drug pyrvinium pamoate has attracted a strong interest for its anti-cancer activity, which has been demonstrated in many cancer models. Considering the previously established inhibitory effect of pyrvinium pamoate on the Wnt/β-catenin pathway and given the important role of this pathway in MM, we investigated the potential anti-tumor activity of this drug in MM cell lines. We observed that pyrvinium pamoate significantly impairs MM cell proliferation, cloning efficiency, migration, and tumor spheroid formation. At the molecular level, our data show that pyrvinium pamoate down-regulates the expression of β-catenin and Wnt-regulates genes. Overall, our study suggests that the repurposing of pyrvinium pamoate for MM treatment could represent a new promising therapeutic approach.

Keywords: Wnt; mesothelioma; pyrvinium pamoate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Drug Repositioning*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Mesothelioma / drug therapy*
  • Mesothelioma / genetics
  • Mesothelioma / pathology
  • Pyrvinium Compounds / pharmacology
  • Pyrvinium Compounds / therapeutic use*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Spheroids, Cellular / drug effects
  • Spheroids, Cellular / metabolism
  • Spheroids, Cellular / pathology
  • Time Factors
  • Wnt Signaling Pathway / drug effects
  • Wnt Signaling Pathway / genetics
  • beta Catenin / metabolism

Substances

  • Pyrvinium Compounds
  • RNA, Messenger
  • beta Catenin
  • pyrvinium