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Niclosamide is a potential candidate for the treatment of chemo-resistant osteosarcoma

Xiaoling Huang1, Wei Wang2, Yong Li3

  • 1Wuhan Fourth Hospital, Department of Pulmonary and Critical Care Medicine, Wuhan, Hubei, China.

Genetics and Molecular Biology
|February 3, 2023
PubMed

Insights

Niclosamide effectively inhibits osteosarcoma cell growth and migration, even in chemo-resistant types. This repurposed drug targets beta-catenin, offering a potential new treatment for bone cancer.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Advanced osteosarcoma treatment relies on chemotherapy, but rapid resistance limits efficacy.
  • Niclosamide, an anthelmintic, shows promising anti-cancer properties.
  • Developing novel therapeutic strategies is crucial for osteosarcoma patients.

Purpose of the Study:

  • To evaluate niclosamide's efficacy against osteosarcoma, including chemo-resistant cells.
  • To elucidate the molecular mechanism of niclosamide's anti-cancer activity.
  • To explore the potential of repurposing niclosamide for osteosarcoma treatment.

Main Methods:

  • In vitro studies on parental and chemo-resistant osteosarcoma cell lines.
  • Assessment of cell proliferation, migration, and apoptosis.
  • Analysis of beta-catenin pathway activity.
  • Toxicity assessment in normal osteoblastic cells.

Main Results:

  • Niclosamide inhibited proliferation and migration while inducing apoptosis in osteosarcoma cells at sub-micromolar concentrations.
  • Chemo-resistant osteosarcoma cells were more sensitive to niclosamide than parental cells.
  • Niclosamide's mechanism involves the inhibition of beta-catenin.
  • Increased beta-catenin activity in chemo-resistant cells correlated with hypersensitivity to niclosamide.

Conclusions:

  • Niclosamide demonstrates significant pre-clinical efficacy against osteosarcoma, including chemo-resistant variants.
  • Beta-catenin inhibition is a key mechanism for niclosamide's action in osteosarcoma.
  • Niclosamide represents a viable candidate for osteosarcoma repurposing, with beta-catenin as a potential therapeutic target to overcome chemo-resistance.

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