title: The impact of pyrvinium pamoate on colon cancer cell viability.
abstract: OBJECTIVE
  The in vitro and in vivo effects of pyrvinium pamoate (PP), a newly identified WNT signaling inhibitor, were evaluated against colon cancer cell lines and primary colon cancer samples.
  
  
  METHODS
  Antiproliferative activity of PP and its effects on protein and RNA levels of WNT targets were evaluated on adenomatous polyposis coli (APC (mut)) and β-catenin(mut) cell lines, one WNT(wt) colon cancer cell line, as well as six primary colon cancer samples with mutant APC in vitro. In addition, the effect of PP on the growth of liver metastasis was examined.
  
  
  RESULTS
  PP blocked colon cancer cell growth in vitro in a dose-dependent manner with great differences in the inhibitory concentration (IC(50)), ranging from 0.6 × 10(-6) to 65 × 10(-6) mol/L for colon cancer cells with mutations in WNT signaling. In addition, PP demonstrated a cytotoxic effect on primary colon cancer samples. A combined cytotoxic effect of PP with 5-fluorouracil (5-FU) was observed for two cell lines. PP decreased messenger RNA (mRNA) and protein levels of known WNT target genes as c-MYC and thereby led to the induction of p21. PP inhibited the migration of HCT116 colon cancer cells in vitro and decreased tumor growth in vivo after intraportal injection of HCT116 cells in nude mice.
  
  
  CONCLUSIONS
  PP displays promising anticancer activity against a broad panel of human colon cancer cell lines, as well as primary colon cancer samples. However, our findings do not demonstrate a predominant cytotoxic effect of PP on colon cancer cells with mutations in WNT signaling.
authors: Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital of Würzburg, Oberdürrbacher Strasse 6, 97080, Würzburg, Germany, wiegering_a@ukw.de.
authors: Armin
authors: A
authors: Wiegering
authors: Friedrich-Wilhelm
authors: FW
authors: Uthe
authors: Melanie
authors: M
authors: Hüttenrauch
authors: Bettina
authors: B
authors: Mühling
authors: Michael
authors: M
authors: Linnebacher
authors: Franziska
authors: F
authors: Krummenast
authors: Christoph-Thomas
authors: CT
authors: Germer
authors: Andreas
authors: A
authors: Thalheimer
authors: Christoph
authors: C
authors: Otto
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005472:Fluorouracil / Q000008:administration & dosage; D017491:Genes, APC / Q000187:drug effects; D064593:Heterografts; D006801:Humans; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000556:secondary; D051379:Mice; D011774:Pyrvinium Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D011774:Pyrvinium Compounds; D051176:beta Catenin; C024631:pyrvinium; D005472:Fluorouracil