title: Bovine herpesvirus VP22 induces apoptosis in neuroblastoma cells by upregulating the expression ratio of Bax to Bcl-2.
abstract: Herpesvirus tegument protein VP22 has been shown to have biotherapeutic potential in tumor gene therapy. Some studies indicate that VP22 may enhance the transfer efficiency of therapeutic proteins by delivering them to more cells while trafficking. Our previous study showed that bovine herpesvirus VP22 (BVP22) enhanced equine herpesvirus thymidine kinase-ganciclovir (Etk-GCV) suicide gene therapy by an unknown intracellular effect. In this study, the interaction between BVP22 and host tumor cells was studied in neuroblastoma NXS2 cells. Cell cycle analysis was performed to determine whether BVP22 possesses biotherapeutic potential by altering the cell cycle, making cells more sensitive to therapeutic genes. As a result, the cell cycle was not affected by the transfection of BVP22 into NXS2 cells. However, cytotoxicity induced by BVP22 was observed in NXS2 cells on the second and third days after transient transfection. Further, analyses of caspase-3 activity and apoptosis suggested that BVP22 induces apoptosis in host tumor cells by upregulating the expression ratio of Bax to Bcl-2.
authors.affiliation: Department of Animal Health and Biomedical Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Qiu
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.forename: Jerome S
authors.initials: JS
authors.lastname: Harms
authors.forename: Jennifer
authors.initials: J
authors.lastname: Friedrichsen
authors.forename: Gary A
authors.initials: GA
authors.lastname: Splitter
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002417:Cattle; D002453:Cell Cycle; D006801:Humans; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D010750:Phosphoproteins / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D017384:Sequence Deletion; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D015678:Viral Structural Proteins / Q000235:genetics / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; C494827:Bax protein, mouse; D010750:Phosphoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D015678:Viral Structural Proteins; D051028:bcl-2-Associated X Protein; C073413:herpes simplex virus type 1 protein VP22; C434023:tegument protein VP22, bovine herpesvirus 1; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases