The Antihelminthic Niclosamide Inhibits Cancer Stemness, Extracellular Matrix Remodeling, and Metastasis through Dysregulation of the Nuclear β-catenin/c-Myc axis in OSCC

Scientific Reports
Lin-Hong WangFan Yang

Abstract

Niclosamide is an oral chlorinated salicylanilide antihelminthic agent with potential anticancer activity suggested in several cancer types, however, its anticancer action and likely molecular mechanism in malignant oral cells remain unclear. In the present study, we demonstrated that ALDH+ human oral squamous cell carcinoma (OSCC) cells are characterized by upregulated expression of the pluripotency transcription factors OCT4, Nanog and Sox2, as well as exhibit enhanced cancer stemness, as demonstrated by enhanced tumorsphere formation. We also showed that niclosamide effectively inhibits activation of the Wnt/β-catenin signaling pathway by targeting multiple components of this pathway, including downregulating the expression β-catenin, Dishevelled 2 (DVL2), phosphorylated glycogen synthase kinase-3β (p-GSK3β) and Cyclin D1, in human OSCC SCC4 and SCC25 cell lines, as well as reduced the formation of primary and secondary tumorspheres. In addition, we showed that niclosamide inhibits the epithelial-to-mesenchymal transition (EMT), migration and colony formation of the OSCC cells, by dose-dependently upregulating E-cadherin and the tissue inhibitor of metalloproteinases 2 (TIMP2) mRNA levels, while reducing the expression level...Continue Reading

References

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Citations

Aug 23, 2020·International Journal of Oral Science·Mohit SharmaRaghu Radhakrishnan
Feb 13, 2019·Frontiers in Microbiology·Andrea Miró-CanturriYounes Smani
Mar 22, 2019·Cancers·Karl KunzelmannRainer Schreiber
May 10, 2020·Cells·Madalena C PintoKarl Kunzelmann
Sep 3, 2020·International Journal of Molecular Sciences·Yongsheng RuanYong-Mi Kim

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Methods Mentioned

BETA
transfection
electrophoresis
immunoprecipitation
acetylation

Software Mentioned

Oncomine
TOPFlash

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