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Induction of Apoptosis by Newcastle Disease Virus Strains AF220 and V4-UPM in Human Promyelocytic Leukemia (HL60) and Human T-Lymphoblastic Leukemia (CEM-SS) Cells

Authors: Siti Aishah Abu Bakar, Madihah Zawawi, Abdul Manaf Ali, Aini Ideris


Newcastle Disease Virus (NDV), an avian paramyxovirus, is a highly contagious, generalised virus disease of domestic poultry and wild birds characterized by gastro-intestinal, respiratory and nervous signs. In this study, it was shown that NDV strain AF2240 and V4-UPM are cytolytic to Human Promyelocytic Leukemia, HL60 and Human T-lymphoblastic Leukemia, CEM-SS cells. Results from MTT cytolytic assay showed that CD50 for NDV AF2240 against HL60 was 130 HAU and NDV V4-UPM against HL60 and CEM-SS were 110.6 and 150.9 HAU respectively. Besides, both strains were found to inhibit the proliferation of cells in a dose dependent manner. The mode of cell death either by apoptosis or necrosis was further analyzed using acridine orange and propidium iodide (AO/PI) staining. Our results showed that both NDV strains induced primarily apoptosis in treated cells at CD50 concentration. In conclusion, both NDV strains caused cytolytic effects primarily via apoptosis in leukemia cells.

Keywords: Apoptosis, Cytolytic, Leukaemia, Newcastle DiseaseVirus

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[1] K. W. Reichard, R. M. Lorence, C. J. Cascino, M. E. Peeples, R. J. Walter, M. B. Fernando, H. M. Reyes and J. A. Greager. "Newcastle disease virus selectively kills human tumor cells," J. Surg. Res., 1992, 52: 448-453.
[2] A. R. Omar, A. Ideris, A. M. Ali, F. Othman, K. Yusoff, J. M. Abdullah et al. "An overview of the development of Newcastle disease virus as an anti-cancer therapy," Malaysian J Med Sci., 2002, 9: 4-12.
[3] D. J. Alexander, "Newcastle disease and other avian Paramyxoviridae infections," in Diseases of Poultry, 10th ed., B. W. Calneck, Ed. Ames, IA: Iowa State University Press, 1997, pp. 541-569.
[4] M. A. Mayo. 2002. "A summary of taxonomic changes recently approved by ICTV". Arch. Virol., 2002, 147: 1655-1666.
[5] D. J. Alexander, "Newcastle disease," in A Laboratory Manual for the Isolation and Identification of Avian Pathogens, 3rd ed., H. G. Purchase, L. H. Arp, C. H. Domermuth and J. E.Pearson, Eds. Kennett Square, PA: American Association of Avian Pathologists, 1989, pp. 114-120.
[6] F. M. Batliwalla, B. A. Bateman, D. Serrano, D. Murray, S. Macphail, V. C. Maino et al. "15-year follow-up of AJCC stage III malignant melanoma patients treated postsurgically with Newcastle disease virus (NDV) oncolysate and determination of alterations in the CD8 T cell Noun 1. CD8 T cell - T cell with CD8 receptor that recognizes antigens on the surface of a virus-infected cell and binds to the infected cell and kill itCD8 cell, cytotoxic T cell, killer cell, killer T cell repertoire," Mol Med., 1998, 4: 783-794.
[7] V. Schirrmacher, A. Griesbach and T. Ahlert. "Anti-tumour effects of Newcastle Disease Virus in vivo: local versus systemic effects," Int J Oncol., 2001, 18 : 945-52.
[8] R. M. Lorence, A. L. Pecora, P. P. Major, S. J. Hotte, S. A. Laurie, M. S. Roberts et al. 2003. "Overview of phase I studies of intravenous administration of PV701, an oncolytic virus," Curr Opin Mol Ther., 2003, 5: 618-624.
[9] P. B. Spradbrow and J. L. Samue, "Oral Newcastle disease vaccine in experimental chickens in Australia," in Newcastle Disease in poultry, J. W. Copland, Ed. ACIAR: Canberra, 1987, pp: 44-49. 1987.
[10] H. Westbury. "Newcastle disease virus: an evolving pathogen," Avian Pathology, 2001, 30: 5-11.
[11] M. C. Lai and A. L. Ibrahim, "Velogenic-viscerotropic Newcastle disease virus," in New castle disease virus in poultry, J.W. Copland Ed. ACIAR Monograph.1987.
[12] W. S. Tan, C. H. Lau, B. K. Ng, A. L. Ibrahim and K. Yusoff. "Nucleotide sequence of the haemagglutinin-neuraminidase (HN) gene of a Malaysian heat resistant viscerotropic-velogenic Newcastle disease virus," DNA Sequence, 1995, 6: 47-50.
[13] K. Yusoff and W. S. Tan. "Newcastle disease virus: macromolecules and opportunities," Avian Pathology, 2001, 30: 439-455.
[14] M. Meyyappan. "Oncolytic effect of Newcastle disease virus on the MCF-7 and MDA-231 breast cancer cell lines," Master Thesis, Universiti Putra Malaysia, Malaysia, 2003.
[15] H. S. M. Wali. "The effects of Newcastle Disease Virus (NDV) on breast cancer cell lines," Master Thesis, Universiti Putra Malaysia, Malaysia, 2003.
[16] M. Aied. "Antileukaemic effect of local Newcastle disease virus strains AF2240 and V4-UPM on leukaemia cell lines in vitro and in vivo," Ph. D Thesis. Universiti Putra Malaysia, Malaysia, 2007.
[17] Rola Ali, Aied M. Alabsi, Abdul Manaf Ali, Aini Ideris , Abdul Rahman Omar and Khatijah Yousoff. "Apoptosis Induction and Cytolytic Effects of Newcastle Disease Virus Strain Af2240 on DBTRG.05 mg Brain Tumor Cell Line." International Journal of Cancer Research, 2011, 7: 25-35.
[18] D. J. Alexander, "Newcastle Disease Diagnosis," in Newcastle Disease, D. J. Alexander, Ed. Kluwer Academic Publishers: Norwell, Massachusetts, 1988, pp: 147-160.
[19] P. Chambers and A. C. R. Samson. "A new structural protein for newcastle disease virus," J. General Virol.1980, 50: 155-166.
[20] K. Yusoff, W. S. Tan, C. H. Lau, B. K. Ng and A. L. Ibrahim. "Sequence of the haemagglutinin-neuraminadase gene of the Newcastle disease virus oral vaccine strain V4 (UPM)," Avian Pathol., 1996, 25: 837-844.
[21] R. M. Lorence, P. A. Rood and K. W. Kelley. "Newcastle disease virus as an antineoplastic agent: induction of tumor necrosis factor-alpha and augmentation of its cytotoxicity," J Natl Cancer Inst., 1988, 80: 1305- 1312.
[22] U. Zorn, I. Dallmann, J. Grosse J. et al. "Induction of cytokines and cytotoxicity against tumor cells by Newcastle disease virus," Cancer Biother., 1994, 9: 225-235.
[23] Y. Tzadok-David, M. Metzkin-Eizenberg, Z. Zakay-Rones. "The effect of a mesogenic and a lentogenic Newcastle disease virus strain on Burkitt lymphoma Daudi cells," J Cancer Res Clin Oncol., 1995, 121: 169-174.
[24] T. Ahlert and V. Schirrmacher. "Isolation of a human melanoma adapted Newcastle disease virus mutant with highly selective replication patterns," Cancer Res., 1990, 50: 5962-5968.
[25] P. V Ravindra, A. K. Tiwari, B. Ratta, U. Chaturvedi, S. K. Palia, P. K. Subudhi et al. "Induction of apoptosis in Vero cells by Newcastle disease virus requires viral replication, de-novo protein synthesis and caspase activation," Virus Res., 2008, 133: 285-290.
[26] B. Washburn, M. A. Weigand, A. Grosse-Wilde, M. Janke, H. Stahl, E. Rieser, M. R. Sprick, V. Schirrmacher and H. Walczak. "TNF-related apoptosis-inducing ligand mediates tumoricidal activity of human monocytes stimulated by Newcastle disease virus," J. Immunol., 2003, 170: 1814-1821.
[27] J. F. R. Kerr, A. H. Wyllie and A. R. Currie. "Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics," Br. J. Cance., 1972, 26: 239-257.
[28] A. H. Wyllie, J. F. R. Kerr and A. R. Currie. "Cell death: the significance of apoptosis," Int. Rev. Cytol., 1980, 68: 251-306.
[29] S. A. Jahanmehr, K. Hyde, C. G. Geary et al. "Simple technique for fluorescence staining of blood cells with acridine orange," J Clin Pathol., 1987, 40: 926-929.
[30] A. J. McGohan, S. J. Martin, R. P. Bissonette, A. Mahboubi, Y. Shi, R. J. Mogil, W. K. Nishioka and D. R. Green, in Methods in Cell Biology, L.M Schwartz and B.A Osborne, Eds. London: Academic Press Incorporated. 1995, pp. 153-185.
[31] K. Mascotti, J. McCullough and S. R. Burger. "HPC viability measurement: Trypan blue versus acridine orange and propidium iodide," Transfusion, 2000, 40: 693-696.