Effects of nuclear factor-κB inhibitors and its implication on natural killer T-cell lymphoma cells

Natural killer/T-cell lymphoma (NKTL) is a highly aggressive disease. Despite the use of various treatment regimens, the prognosis of NKTL is poor, and new treatment strategies need to be determined. Because of the significant survival potential, nuclear factor (NF)-κB has become one of the major targets for drug development. In this study, we explored the effect and action mechanism of NF-κB inhibitors, BAY 11-7082 and curcumin, on NKTL cell lines (NKL, NK-92 and HANK1). Electrophoretic mobility shift assay showed that NF-κB was constitutively active in HANK1, a chemoresistant cell line. BAY 11-7082 and curcumin suppressed NF-κB activation in a time- and dose-dependent manner, which finally resulted in cell death. BAY 11-7082- and curcumin-induced cell death was associated with downregulation of Bcl-x _L, cyclin D1, XIAP and c-FLIP, followed by caspase-8, poly(ADP-ribose) polymerase cleavage and activation. Given that the chemoresistant NK-92 cells respond to NF-κB inhibitors but not to conventional drugs, BAY 11-7082 and curcumin could be potentially useful for achieving improved outcome in chemotherapy-refractory NKTL.