NF-κ B Inhibition Causes Spontaneous Apoptosis in Epstein-Barr Virus-Transformed Lymphoblastoid Cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 97; no. 11; pp. 6055 - 6060
• Main Authors: Cahir-McFarland, Ellen D., Davidson, David M., Schauer, Stephanie L., Duong, Jimmy, Kieff, Elliott
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 23.05.2000; National Acad Sciences; The National Academy of Sciences
• Subjects: Amino Acid Chloromethyl Ketones - pharmacology; Antibodies; Apoptosis; Apoptosis - physiology; B lymphocytes; B-Lymphocytes - cytology; B-Lymphocytes - virology; Biological Sciences; Caspase 3; Caspase 8; Caspase 9; Caspase Inhibitors; Caspases - metabolism; Cell Cycle - drug effects; Cell extracts; Cell growth; Cell Line, Transformed - cytology; Cell lines; Cell Transformation, Viral; Cysteine Proteinase Inhibitors - pharmacology; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Drug Design; Epstein Barr virus infections; Epstein-Barr virus; Flow Cytometry; Gene Expression Regulation; Herpesvirus 4, Human - physiology; Humans; I-kappa B Proteins; I^KB^a protein; IBa protein; Intracellular Membranes - physiology; Lymphoproliferative Disorders - drug therapy; Lymphoproliferative Disorders - virology; Membrane Potentials; Microscopy, Confocal; Minor Histocompatibility Antigens; Mitochondria - physiology; Mitochondrial membranes; NF-^KB protein; NF-B protein; NF-kappa B - antagonists & inhibitors; NF-kappa B - physiology; NF-KappaB Inhibitor alpha; Notch protein; Plasmids; Protein Biosynthesis; Proteins - genetics; Proto-Oncogene Proteins c-bcl-2; Recombinant Fusion Proteins - physiology; T lymphocytes; Transfection
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.100119497

Epstein-Barr virus (EBV) transforms B lymphocytes into lymphoblastoid cell lines usurping the Notch and tumor necrosis factor receptor pathways to effect transcription including NF-κ B activation. To determine whether NF-κ B activity is essential in the growth and survival of EBV-transformed lymphoblastoid cell lines, a nondegradable Iκ Bα mutant was expressed under tetracycline regulation. Despite continued Bcl-2 and Bcl-x/L expression, NF-κ B inhibition induced apoptosis as evidenced by poly(ADP-ribose) polymerase cleavage, nuclear condensation and fragmentation, and hypodiploid DNA content. Both caspase 3 and 8 activation and loss of mitochondrial membrane potential were observed in apoptotic cells. However, caspase inhibition failed to block apoptosis. These experiments indicate that NF-κ B inhibitors may be useful in the therapy of EBV-induced cellular proliferation.