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ORIGINAL RESEARCH article
Front. Oncol.
Sec. Pediatric Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1508819
Repurposing Riluzole as an anti-osteosarcoma agent
Provisionally accepted
Okkeun Jung1
Vinagolu K. Rajasekhar2
Syeda Maryam Azeem1Shraddha ChandThakuri3Beatrice Norton3
John Healey2*
Shahana Mahajan3*- 1The Graduate Center,The City University of New York, New York City, New York, United States
- 2Memorial Sloan Kettering Cancer Center, New York, New York, United States
- 3Hunter College (CUNY), New York City, United States
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We have studied riluzole, a glutamate-release inhibitor, as a novel anti-osteosarcoma agent. YAP (Yes-associated protein) is recruited by Bax promoter to stimulate its expression during riluzoleinduced apoptosis in the human metastatic osteosarcoma cell line LM7. Given the substantial genetic heterogeneity in osteosarcoma, studies on the efficacy of riluzole in diverse osteosarcomas will be an asset in developing preclinical studies. Toward this goal, we investigated the effects of riluzole on 11 osteosarcoma cell lines derived from primary or metastatic tumors of mouse or human origin and on four independent patient-derived xenograft (PDX) tumor cell lines. We found that most of the osteosarcoma cell lines, including PDX cell lines secrete glutamate and exhibit invasive abilities.Cell growth and invasive ability of all the cell lines and PDX cell lines are inhibited by riluzole.Additionally, riluzole suppresses the activity of matrix metalloprotease-2 (MMP2) in most of the osteosarcoma cell lines (but not the PDX cells). These results suggest that riluzole's inhibitory effects on osteosarcoma invasion may in part be attributable to the inhibition of MMP2 activity, and that riluzole is potentially an effective agent for inhibiting growth of primary and metastatic osteosarcomas with a wide range of genetic profiles.
Keywords: Osteosarcoma, Riluzole, Reactive Oxygen Species, MMP2, metastasis, Patientderived xenograft
Received: 09 Oct 2024; Accepted: 08 Apr 2025.
Copyright: © 2025 Jung, Rajasekhar, Azeem, ChandThakuri, Norton, Healey and Mahajan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
John Healey, Memorial Sloan Kettering Cancer Center, New York, NY 10065, New York, United States
Shahana Mahajan, Hunter College (CUNY), New York City, United States
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