Osteosarcoma growth suppression by riluzole delivery via iron oxide nanocage in nude mice

Abstract

Osteosarcomas are the most commonly occurring malignant bone cancer in young individuals. The survival rate of patients with metastatic osteosarcoma is low and has been stagnant for over two decades. We previously demonstrated that the glutamate release inhibitor, riluzole inhibits osteosarcoma cell growth. Towards the development of more effective therapy, we investigated the delivery of riluzole in human metastatic osteosarcoma xenografts in mice. We compared the efficacy of riluzole delivery by intraperitoneally injecting either free riluzole or riluzole released via two different shapes of iron oxide nanoparticles (nanocage or nanosphere) of size 15±2.5 nm. We monitored tumor size using Vernier calipers and bioluminescence assay and found a significant reduction in tumor size in the riluzole-treated groups when injected, either in free form or via nanoparticles, compared to the control groups (PBS, nanosphere or nanocage). Importantly, nanocage-delivered riluzole was most effective in reducing tumor size in the xenograft nude mice. While riluzole delivery induced apoptosis in tumor tissues in all three groups of riluzole-treated animals, it was highest in tumors from the nanocage-delivered riluzole group. Therefore, we conclude that riluzole is an effective drug to reduce tumor size in osteosarcoma and the efficacy of riluzole as a apoptotic and tumor-reducing drug is enhanced when delivered via nanocage.

miR-497 inhibits tumor growth and migration of osteosarcoma by targeting plexinA4 and CDK6

“…e treatments for osteosarcoma include surgery, radiotherapy, chemotherapy, or a combination of modalities. Despite improvements in diagnostic and therapeutic techniques, the 5-year survival rates for patients with osteosarcoma have not increased over the last 20 years [3,4]. e potentially high incidence of morbidity and low cure rate urgently require novel methods for diagnosing and treatments which rely on biomedical research.…”

Riluzole: A neuroprotective drug with potential as a novel anti‑cancer agent (Review)

“…Riluzole-mediated YAP and P73 complex was reported to activate Bax promoter to regulate pro-apoptotic activity (55). Previous studies by our group also suggested that iron oxide nanoparticle-delivered riluzole induced apoptosis in vitro in osteosarcoma cells and shrunk osteosarcoma tumors in a xenograft mouse model (72,73). Since apoptosis ultimately leads to the elimination of cancer cells, a better understanding of the induction of riluzole-mediated cell death, the effects of riluzole on different cellular processes and how they are related to apoptosis may further improve the use of riluzole in different cancer types.…”

Riluzole-induced apoptosis in osteosarcoma is mediated through Yes-associated protein upon phosphorylation by c-Abl Kinase

“…Although Riluzole induces apoptosis in osteosarcoma in the xenograft mouse model, it needs to be determined if Riluzole activates c-Abl kinase and phosphorylates YAP at Y357 to induce apoptosis in vivo 58 . Riluzole has been shown to induce apoptosis through ER stress in prostate cancer cell lines 15 .…”