Niclosamide and pyrvinium are both potential therapeutics for osteosarcoma, inhibiting wnt–axin2–snail cascade

Young Yi, Young Mi Woo, Kyu Ho Hwang, Hyun Sil Kim, Sang Hyeong Lee

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Osteosarcoma, the most common primary bone malignancy, is typically related to growth spurts during adolescence. Prognosis is very poor for patients with metastatic or recurrent osteosarcoma, with survival rates of only 20–30%. Epithelial–mesenchymal transition (EMT) is a cellular mechanism that contributes to the invasion and metastasis of cancer cells, and Wnt signaling activates the EMT program by stabilizing Snail and β‐catenin in tandem. Although the Wnt/Snail axis is known to play significant roles in the progression of osteosarcoma, and the anthelmintic agents, niclosamide and pyrvinium, have been studied as inhibitors of the Wnt pathway, their therapeutic effects and regulatory mechanisms in osteosarcoma remain unidentified. In this study, we show that both niclosamide and pyrvinium target Axin2, resulting in the suppression of EMT by the inhibition of the Wnt/Snail axis in osteosarcoma cells. Axin2 and Snail are abundant in patient samples and cell lines of osteosarcoma. The treatment of niclosamide and pyrvinium inhibits the migration of osteosarcoma cells at nanomolar concentrations. These results suggest that Axin2 and Snail are candidate therapeutic targets in osteosarcoma, and that anthelminthic agents, niclosamide and pyrvinium, may be effective for osteosarcoma patients.

Original languageEnglish
Article number4630
JournalCancers
Volume13
Issue number18
DOIs
Publication statusPublished - 2021 Sep

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation of Korea (NRF‐2021R1A2C3003496) funded by the Korean government (MSIP).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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