Antiproliferative and Apoptotic Effect of Newcastle Disease Virus (NDV) Strain AF2240 in Human Promyelocytic Leukemia Cells (HL60)
Background: Newcastle Disease Virus (NDV) is a negative-sense single stranded RNA virus that causes a Newcastle Disease (ND), a contagious disease of domestic poultry and wild birds characterized by gastro-intestinal, respiratory and nervous signs. Despite the negative effects of NDV to avian specie...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
2016
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| Subjects: | |
| Online Access: | http://eprints.unisza.edu.my/5153/1/FH02-FBIM-17-08443.pdf http://eprints.unisza.edu.my/5153/ |
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| Summary: | Background: Newcastle Disease Virus (NDV) is a negative-sense single stranded RNA virus that causes a Newcastle Disease (ND), a contagious disease of domestic poultry and wild birds characterized by gastro-intestinal, respiratory and nervous signs. Despite the negative effects of NDV to avian species, this virus was reported to possess significant oncolytic activity against mammalian cancerous cells. Methodology: In this study, the antiproliferative and apoptotic effect of NDV strain AF2240 on human promyelocytic leukaemia FIL60 cell line were assessed using M7 proliferation assay, microscopic observation, DNA fragmentation, annexin V-FITC assay, caspase-3/7, 8, 9 assays and caspase-3/7, 8, 9 inhibition assays. Results: The proliferation of FIL60 cells was inhibited when treated with cytotoxic titers (CD25. CDso and CD,5) of NDV AF2240 for a period of 72 h. Result from microscopic observation showed NDV AF2240 caused inhibition of cell growth and the treated cells exhibited morphological features of apoptosis and a ladder-like pattern of DNA, which is a hallmark of apoptosis. The proportion of cells in early and late apoptosis was quantified by using annexin V-FITC staining and analysed with flow cytometer. The percentage of cells in early apoptosis after treatment with NDV AF2240 at CDs° titer for 24 and 48 h were 16.27±0.25 and 25.93 ± 1.2%, respectively. Late-apoptotic cells were increased from 3.15±0.07 and 6.85 ±1.05%, respectively. The mechanism of apoptosis through activation of caspases induced by NDV AF2240 was also analysed. The results suggested that apoptosis in NDV-infected tumor cells is dependent on caspase as both iniatiator caspases; caspase 8 and 9 were activated. Activation of caspase-3/7 were also detected in the cells treated with NDV AF2240. Furthermore, apoptosis by NDV AF2240 was effectively inhibited by ZVAD-FMK indicate that NDV AF2240-induced apoptosis is entirely dependent on caspase activation. Conclusion: To conclude, NDV AF2240 was found to have antiproliferative and apoptotic effects on H L60 cells. It has been shown from this study that NDV AF2240 infection resulted in the activation of both intrinsic and extrinsic apoptotic pathways' |
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