Repurposing riluzole as an anti-osteosarcoma agent
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 riluzole-induced apoptosis in the human metastatic osteosarcoma cell line LM7. Given the substantial genetic heter...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1508819/full |
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| author | Okkeun Jung Vinagolu K. Rajasekhar Syeda Maryam Azeem Shraddha ChandThakuri Beatrice Norton John H. Healey Shahana Mahajan Shahana Mahajan Shahana Mahajan Shahana Mahajan |
| author_facet | Okkeun Jung Vinagolu K. Rajasekhar Syeda Maryam Azeem Shraddha ChandThakuri Beatrice Norton John H. Healey Shahana Mahajan Shahana Mahajan Shahana Mahajan Shahana Mahajan |
| author_sort | Okkeun Jung |
| collection | DOAJ |
| description | 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 riluzole-induced 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. |
| format | Article |
| id | doaj-art-56673f3dda174d28860b50124a68db34 |
| institution | DOAJ |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-56673f3dda174d28860b50124a68db342025-08-20T03:11:09ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-05-011510.3389/fonc.2025.15088191508819Repurposing riluzole as an anti-osteosarcoma agentOkkeun Jung0Vinagolu K. Rajasekhar1Syeda Maryam Azeem2Shraddha ChandThakuri3Beatrice Norton4John H. Healey5Shahana Mahajan6Shahana Mahajan7Shahana Mahajan8Shahana Mahajan9Program in Biology, The CUNY Graduate Center, New York, NY, United StatesOrthopedic Research Laboratory, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, United StatesProgram in Biology, The CUNY Graduate Center, New York, NY, United StatesDepartment of Medical Laboratory Sciences, Hunter College, City University of New York, New York, NY, United StatesDepartment of Chemistry at Hunter College, City University of New York, New York, NY, United StatesOrthopedic Research Laboratory, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, United StatesProgram in Biology, The CUNY Graduate Center, New York, NY, United StatesDepartment of Medical Laboratory Sciences, Hunter College, City University of New York, New York, NY, United StatesProgram in Biochemistry, The CUNY Graduate Center, New York, NY, United StatesBrain Mind Research Institute, Weill Cornell Medical College, New York, NY, United StatesWe 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 riluzole-induced 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.https://www.frontiersin.org/articles/10.3389/fonc.2025.1508819/fullosteosarcomariluzolereactive oxygen speciesMMP2metastasispatient-derived xenograft cell lines |
| spellingShingle | Okkeun Jung Vinagolu K. Rajasekhar Syeda Maryam Azeem Shraddha ChandThakuri Beatrice Norton John H. Healey Shahana Mahajan Shahana Mahajan Shahana Mahajan Shahana Mahajan Repurposing riluzole as an anti-osteosarcoma agent Frontiers in Oncology osteosarcoma riluzole reactive oxygen species MMP2 metastasis patient-derived xenograft cell lines |
| title | Repurposing riluzole as an anti-osteosarcoma agent |
| title_full | Repurposing riluzole as an anti-osteosarcoma agent |
| title_fullStr | Repurposing riluzole as an anti-osteosarcoma agent |
| title_full_unstemmed | Repurposing riluzole as an anti-osteosarcoma agent |
| title_short | Repurposing riluzole as an anti-osteosarcoma agent |
| title_sort | repurposing riluzole as an anti osteosarcoma agent |
| topic | osteosarcoma riluzole reactive oxygen species MMP2 metastasis patient-derived xenograft cell lines |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1508819/full |
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