Repurposing riluzole as an anti-osteosarcoma agent Journal Article
| Authors: | Jung, O.; Rajasekhar, V. K.; Azeem, S. M.; ChandThakuri, S.; Norton, B.; Healey, J. H.; Mahajan, S. |
| Article Title: | Repurposing riluzole as an anti-osteosarcoma agent |
| Abstract: | 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. Copyright © 2025 Jung, Rajasekhar, Azeem, ChandThakuri, Norton, Healey and Mahajan. |
| Keywords: | osteosarcoma; controlled study; unclassified drug; human cell; cisplatin; doxorubicin; methotrexate; antineoplastic agent; gene; metastasis; cell growth; etoposide; antineoplastic activity; ifosfamide; western blotting; reactive oxygen species; reactive oxygen metabolite; real time polymerase chain reaction; glutamic acid; cell invasion; rna extraction; genetic heterogeneity; gelatinase a; growth inhibition; p53 gene; zymography; cdkn2a gene; riluzole; fgfr3 gene; human; article; vegfa gene; drug repositioning; osteosarcoma cell line; mtt assay; dot1l gene; u2os cell line; notch4 gene; saos-2 cell line; ccnd3 gene; k7m2-wt cell line; mg-63 cell line; mmp2; patient-derived xenograft cell lines; anti-osteosarcoma agent; hos gene; hos-mnng cell line; metastatic osteosarcoma cell line lm7; mg63.3 cell line; mmp9 gene; mnng gene; nbn1 gene; ncor1 gene; os24 cell line; os29 cell line; os33 cell line; os482 cell line; os69 cell line |
| Journal Title: | Frontiers in Oncology |
| Volume: | 15 |
| ISSN: | 2234-943X |
| Publisher: | Frontiers Media S.A. |
| Date Published: | 2025-01-01 |
| Start Page: | 1508819 |
| Language: | English |
| DOI: | 10.3389/fonc.2025.1508819 |
| PROVIDER: | scopus |
| PMCID: | PMC12086166 |
| PUBMED: | 40391158 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is John H. Healey -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work