Induction of apoptosis by a Newcastle disease virus vaccine (MTH-68/H) in PC12 rat phaeochromocytoma cells.
The attenuated Newcastle Disease Virus (NDV) vaccine MTH-68/H has been found to cause regression of various tumors including certain types of human neoplasms (See Table 1 and References 86-88). The mechanism of its oncolytic action is poorly understood, but it appears to affect specific signaling pathways in the target cell. We studied the cellular effects of NDV employing PC12 rat phaeochromocytoma cells, a widely used model system to analyze differentiation, proliferation and apoptosis. The MTH-68/H vaccine was found to be cytotoxic on PC12 cells. It caused internucleosomal DNA fragmentation, the most characteristic feature of programmed cell death (PCD). A brief exposure (30 min) of P12 cells to the virus was sufficient to produce a full-blown apoptotic response. Major mitogen-activated protein kinase pathways (including the stress inducible c-Jun N-terminal kinase pathway and p38 pathway) or mechanisms regulated by reactive oxygen species appear to have no role in virus-induced cell death. The PCD-inducing effect of MTH-68/H could not be prevented by simultaneous treatment of the P12 cells with growth factors or second messenger analogs stimulating protein kinase C or Ca(++)-mediated pathways. In contrast, treatment with a cyclic AMP analog partially protected the them from virus-induced apoptosis. These experimental results suggests that MTH-68/H might disrupt a growth factor-stimulated survival pathway and that direct stimulation of protein kinase A-catalyzed phosphorylation events bypass this NDV-induced block.
Fábián
Z
Z
Department of Medical Biology, Faculty of Medicine, Pécs University, Hungary.
Töröcsik
B
B
Kiss
K
K
Csatary
L K
LK
Bodey
B
B
Tigyi
J
J
Csatary
C
C
Szeberényi
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003994:Bucladesine / Q000494:pharmacology; D019496:Cancer Vaccines / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000648:ultrastructure; D002675:Child, Preschool; D053938:DNA Fragmentation / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009522:Newcastle disease virus / Q000276:immunology*; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014765:Viral Vaccines / Q000494:pharmacology* / Q000633:toxicity
D019496:Cancer Vaccines; D006133:Growth Substances; C424862:Newcastle disease virus vaccine MTH-68-H; D017382:Reactive Oxygen Species; D014765:Viral Vaccines; D003994:Bucladesine; D020928:Mitogen-Activated Protein Kinases