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.
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-cateninmut cell lines, one WNTwt 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.
PP blocked colon cancer cell growth in vitro in a dose-dependent manner with great differences in the inhibitory concentration (IC50), 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.
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.
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The work was supported by the German Research Foundation (DFG), grant 1516/2-1 (to AT), and by funds from the Interdisciplinary Centre for Clinical Research (IZKF) of the University of Würzburg (B-121 to AT and B-186 to AW). The authors assume full responsibility for the contents of the research. This publication was funded by the German Research Foundation (DFG), and the University of Würzburg is in the funding program Open Access Publishing.
Conflict of interest
The authors declare no conflict of interest.
Conceived and designed the experiments: AW, AT, FK, CTG, ML, CO; performed the experiments: AW, FWU, MH, BM, ML, CO. Analyzed the data: AW, FWU, MH, BM, AT, CO; contributed reagents/materials/analysis tools: AW, FWU, MH, BM, ML, CTG, FK; wrote the paper: AW, CTG, FK, AT, CO.
AT and CO contributed equally to this work
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Wiegering, A., Uthe, F., Hüttenrauch, M. et al. The impact of pyrvinium pamoate on colon cancer cell viability. Int J Colorectal Dis 29, 1189–1198 (2014). https://doi.org/10.1007/s00384-014-1975-y
- Pyrvinium pamoate
- Colon cancer cell lines
- WNT pathway