Newcastle Disease Virus-induced Apoptosis in PC12 Pheochromocytoma Cells

Abstract

The avian paramyxovirus Newcastle disease virus (NDV) causes severe infections in birds. It is essentially nonpathogenic in rodents and human beings but was found to have an oncolytic potential against certain types of human malignancies. An attenuated NDV vaccine (designated MTH-68/H) was found to cause regression of various human tumors, but the mechanism of its oncolytic action and its selectivity toward malignant cells remain poorly understood. NDV was reported to cause apoptotic death in several avian cultured cell types. Programmed cell death may thus be the basis for the oncolytic effect of NDV vaccines. To test this possibility, we chose the PC12 rat pheochromocytoma cell line, a widely used model system for apoptosis. The MTH-68/H vaccine was found to cause apoptotic death of PC12 cells in a dose-dependent manner. A brief exposure of cells to the virus was found to trigger the apoptotic response. Cell death induced by the vaccine was not accompanied by significant alterations in the major mitogen-activated protein kinase pathways of these cells. Apoptotic DNA fragmentation was not affected by stimulating growth factor pathways or signaling mechanisms mediated by protein kinase C or the second messenger, calcium. In contrast, stimulation of protein kinase A by cyclic adenosine monophosphate analogs gave partial protection against the virus. PC12 cells thus provide a useful model system to study the effects of NDV on cell survival at the molecular level.

p53-Independent Endoplasmic Reticulum Stress-Mediated Cytotoxicity of a Newcastle Disease Virus Strain in Tumor Cell Lines

“…In these early trials, different NDV isolates were effective in human tumors as diverse as hematological tumors, gastrointestinal cancers, and glioblastomas. NDV was also found to be cytotoxic for cultures of transformed avian and mammalian cells (19,45,53).…”

Selective gene transfer to tumor cells by recombinant Newcastle Disease Virus via a bispecific fusion protein

“…All FACS data were analyzed with CELLQuest software (Becton Dickinson, Heidelberg, Germany). 6 ) were washed twice with FCS-free RPMI-1640 medium and then incubated with MG132 (Calbiochem  , Germany) at a final concentration of 50 µM for 1 h at 37˚C. Without washing, the treated cells were infected by NDV using the standard protocol as described above.…”

“…Human erythrocytes were isolated from buffy coat by centrifugating at 600 x g and then washed with 3-fold volume of isotonic PBS. Erythrocytes (1x10 6 ) were coincubated with NDV for 1 h using the above described protocol and analysed with flow cytometry. NA activity of HN proteins of NDV was also determined by flow cytometry.…”

“…NA activity of HN proteins of NDV was also determined by flow cytometry. Briefly, 1x10 6 erythrocytes were co-incubated with NDV for 1 h at 37˚C. After 2 washes in PBS, the erythrocytes were incubated with 3.1 µg/ml peanut agglutinin (PNA)-FITC (Sigma, Munich, Germany) for 30 min at room temperature and then analysed by FACS analysis.…”

“…Newcastle Disease Virus (NDV), a negative-strand RNA virus belonging to the family Paramyxoviridae, shows tumor selective replication, which leads to tumor apoptosis and death (4)(5)(6). Two main properties of this virus are very interesting.…”