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Apoptosis-inducing activity and growth suppression by vesnarinone on human glioma transplanted in nude mice
1Institute of Neurological Sciences, Faculty of Medicine, Tottori University School of Medicine, Yonago, Japan.
Abstract:
The growth and morphological change of human glioma transplanted subcutaneously and intracerebrally to nude mice with orally administered vesnarinone, 3,4-dihydro-6-[4-(3,4-dimethoxy-benzoyl)-1-piperazinyl]-2(1H)-quinolinon e, were examined. The tumor volume of human glioma xenograft, GL-9, subcutaneously transplanted to nude mice, was significantly decreased by orally administered vesnarinone at a dose of 500 mg kg-1. Vesnarinone also significantly prolonged the survival of nude mice transplanted intracerebrally with GL-9. Apoptosis was observed in paraffin sections of both subcutaneous and intracerebral GL-9 by the method of direct immunoperoxidase detection of digoxigenin-dUTP-labeled nick ends introduced by terminal deoxynucleotidyl transferase. These findings suggest that vesnarinone suppresses the growth and induces apoptosis of glioma cells in vivo.
Insights
The drug vesnarinone significantly reduced human glioma xenograft growth in mice and prolonged survival. This suggests vesnarinone may suppress glioma progression by inducing apoptosis in tumor cells.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Human glioma xenografts are utilized in preclinical research to evaluate anti-cancer agents.
- Vesnarinone is an investigational drug with potential anti-tumor properties.
Purpose of the Study:
- To investigate the efficacy of orally administered vesnarinone on human glioma xenograft growth and survival in nude mice.
- To determine if vesnarinone induces apoptosis in glioma cells in vivo.
Main Methods:
- Human glioma (GL-9) xenografts were transplanted subcutaneously and intracerebrally into nude mice.
- Mice received oral administration of vesnarinone at 500 mg kg-1.
- Tumor volume and animal survival were monitored.
- Apoptosis was assessed using direct immunoperoxidase detection of digoxigenin-dUTP-labeled nick ends.
Main Results:
- Oral administration of vesnarinone significantly decreased the tumor volume of subcutaneous human glioma xenografts.
- Vesnarinone significantly prolonged the survival of mice with intracerebral glioma xenografts.
- Apoptosis was observed in both subcutaneous and intracerebral GL-9 xenografts treated with vesnarinone.
Conclusions:
- Vesnarinone demonstrates significant anti-tumor activity against human glioma xenografts in vivo.
- The findings suggest that vesnarinone suppresses glioma cell growth and induces apoptosis, supporting its potential as a therapeutic agent.