Newcastle Disease Virus vaccine-induced apoptotic cell death of PC12 cells

J. Szeberenyi a, Z. Fabian a, K. Kiss a, B. Torocsik a, and L.K. Csatary b

aDepartment of Medical Biology, Medical School, University of Pecs, Pecs, Hungary; bUnited Cancer Research Institute, Ft. Lauderdale, FL, USA

The attenuated Newcastle disease virus vaccine MTH-68/H used in veterinary medicine was found earlier to be an effective oncolytic agent in several human clinical trials. The present studies were initiated to characterize the direct cytotoxic effect of MTH-68/H in a tumor cell line (PC12 phaeochromocytoma cells) as cell culture model system. MTH-68/H was found to induce apoptotic DNA fragmentation in PC 12 cells. The activity of the major mitogen-activated protein kinase pathways (ERK, JNK and p 38 MAPK pathway), as assessed by Western blotting using anti-MAPK antibodies specific for the phosphorylated forms of MAPK isozymes, were not affected by MTH-68/H treatment. Stimulation by growth factors (NGF, FGF, EGF) that prevent serum starvation induced apoptosis did not inhibit vaccine-stimulated DNA fragmentation. In contrast, activation of protein kinase A mediated mechanisms by a camp analog gave partial protection against the cytotoxic effect of the virus. PC12 cells thus may provide a useful model to identify and characterize the targets of Newcastle disease virus in tumor cells.

KEY WORDS: mitogen activated protein kinase (MAPK), .

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Apoptosis - Molecular Mechanisms.