NF-kappa B inhibition causes spontaneous apoptosis in Epstein-Barr virus-transformed lymphoblastoid cells

Epstein-Barr virus (EBV) transforms B lymphocytes into lymphoblastoid cell lines usurping the Notch and tumor necrosis factor receptor pathways to eff ect transcription including NF-kappa B activation. To determine whether NF- kappa B activity is essential in the growth and survival of EBV-transformed lymphoblastoid cell lines, a nondegradable I kappa B alpha mutant was expr essed under tetracycline regulation. Despite continued Bcl-2 and Bcl-x/L ex pression, NF-kappa B inhibition induced apoptosis as evidenced by poly(ADP- ribose) polymerase cleavage, nuclear condensation and fragmentation, and hy podiploid DNA content. Both caspase 3 and 8 activation and loss of mitochon drial membrane potential were observed in apoptotic cells, However, caspase inhibition failed to block apoptosis, These experiments indicate that NF-k appa B inhibitors may be useful in the therapy of EBV-induced cellular prol iferation.