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Newcastle diseases virus strain V4UPM displayed oncolytic ability against experimental human malignant glioma
M M Zulkifli1, R Ibrahim, A M Ali
1Department of Neurosciences, School of Medical Science, University Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia. JeoCity_vet@yahoo.com
Introduction:
Newcastle disease virus (NDV) is a virus of paramyxovirus family and lately has been studied for the treatment of cancer in human. In this study, we successfully determined the oncolysis potential of NDV vaccine, V4UPM tested on the human glioblastoma multiform cell line (DBTRG.05MG) and human glioblastoma astrocytoma cell line (U-87MG) in vitro and in vivo. The V4UPM strain is a modified V4 strain developed as thermostable feed pellet vaccine for poultry.
Objective:
The objectives of this study were mainly to evaluate the cytolytic effect and subsequently determine the brain tumor regression potential induced by this strain in athymic mice model.
Methodology And Results:
V4UPM, the avirulent strain of NDV, was propagate and screened for the cytolytic activity towards DBTRG.05MG and U-87MG using MTT assay. The inhibition concentration 50% (IC(50)) values by monolayer method measured at hour 72 were 23 and 9 HAU/ml, respectively. Further study was carried out to observe an apoptosis of the infected cells by AO/PI staining and revealed the apoptosis features of the treated cells. Subcutaneous human brain tumors grown on the nude mice were treated by V4UPM at IC(80) and complete regression of U-87MG-bearing tumor mice was observed. TUNEL assay analysis of treated tumor tissues from treated mice showed an occurrence of apoptosis.
Conclusion:
From this study, NDV strain V4UPM inhibits the proliferation of experimental human gliomas in tissue culture and IC(80) at 520 HAU V4UPM gives potent effect to induced tumor regression and apoptosis in malignant gliomas.
Insights
Newcastle disease virus (NDV) vaccine V4UPM effectively reduced human glioblastoma cell proliferation in vitro and induced significant tumor regression and apoptosis in vivo, showing potential for brain cancer treatment.
Area of Science:
- Oncology
- Virology
- Biotechnology
Background:
- Newcastle disease virus (NDV), a paramyxovirus, is being investigated for human cancer therapy.
- The V4UPM strain, a modified thermostable NDV vaccine for poultry, was assessed for its oncolytic properties.
Purpose of the Study:
- To evaluate the cytolytic effects of the NDV V4UPM strain on human glioblastoma cell lines (DBTRG.05MG and U-87MG) in vitro.
- To determine the brain tumor regression potential of V4UPM in an athymic mice model.
Main Methods:
- MTT assay was used to determine the 50% inhibitory concentration (IC50) of V4UPM against glioblastoma cells.
- Apoptosis was assessed using AO/PI staining in vitro and TUNEL assay in vivo.
- Tumor regression was evaluated in nude mice bearing subcutaneous human glioblastoma xenografts.
Main Results:
- V4UPM demonstrated significant cytolytic activity against DBTRG.05MG and U-87MG cells, with IC50 values of 23 and 9 HAU/ml, respectively.
- Treatment with V4UPM induced apoptosis in glioblastoma cells in vitro and in tumor tissues.
- Complete regression of U-87MG-bearing tumors was observed in mice treated with V4UPM at IC80.
Conclusions:
- The NDV V4UPM strain effectively inhibits human glioma cell proliferation in vitro.
- V4UPM at IC80 (520 HAU) demonstrates potent tumor regression and apoptosis-inducing effects in malignant gliomas.
- NDV V4UPM shows promise as an oncolytic agent for brain tumor treatment.
