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Related Experiment Video

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Repurposing riluzole as an anti-osteosarcoma agent.

Okkeun Jung1, Vinagolu K Rajasekhar2, Syeda Maryam Azeem1

  • 1Program in Biology, The CUNY Graduate Center, New York, NY, United States.

Frontiers in Oncology
|May 20, 2025
PubMed
Summary

Riluzole, a glutamate-release inhibitor, effectively inhibits osteosarcoma cell growth and invasion across diverse cell lines. It shows potential as an anti-osteosarcoma agent by suppressing matrix metalloprotease-2 activity.

Keywords:
MMP2metastasisosteosarcomapatient-derived xenograft cell linesreactive oxygen speciesriluzole

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Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Osteosarcoma exhibits significant genetic heterogeneity, complicating treatment strategies.
  • Glutamate signaling plays a role in osteosarcoma progression and invasion.
  • Riluzole, a glutamate-release inhibitor, is explored for its anti-cancer potential.

Purpose of the Study:

  • To evaluate the efficacy of riluzole as a novel anti-osteosarcoma agent.
  • To investigate riluzole's effects on diverse osteosarcoma cell lines, including patient-derived xenografts (PDX).
  • To elucidate the mechanisms underlying riluzole's anti-tumor activity.

Main Methods:

  • Tested riluzole's effects on 11 osteosarcoma cell lines and 4 PDX cell lines.
  • Assessed glutamate secretion and invasive abilities of cell lines.
  • Measured effects of riluzole on cell growth, invasion, and matrix metalloprotease-2 (MMP2) activity.

Main Results:

  • Most osteosarcoma cell lines and PDX cells secreted glutamate and were invasive.
  • Riluzole significantly inhibited cell growth and invasion in all tested cell lines.
  • Riluzole suppressed MMP2 activity in most osteosarcoma cell lines, but not in PDX cells.

Conclusions:

  • Riluzole demonstrates broad efficacy against diverse osteosarcoma cell lines, including primary and metastatic types.
  • Inhibition of MMP2 activity may contribute to riluzole's anti-invasive effects.
  • Riluzole is a promising candidate for preclinical studies in osteosarcoma treatment.