NF‐kB inhibition as a strategy to enhance etoposide‐induced apoptosis in K562 cell line

NF‐kB is a transcription factor that mediates antiapoptotic signals in several cancer cell lines. Here we have demonstrated that the cytotoxic drug, Etoposide, activates NF‐kB in K562, a chronic myeloid leukemia blast crisis cell line. Treatment with the NF‐kB inhibitors MG‐132, Bay11‐7082, and Resveratrol impedes Etoposide‐induced NF‐kB activation, rendering K562 sensitive to Etoposide‐induced apoptosis. Stable expression of mutant form of IkB‐α, which retains NF‐kB inactive in the cytoplasm of cells, confirmed the data obtained with molecular inhibitors. Both inhibitors and stable expression of SR‐IkB are associated with down‐modulation of the antiapoptotic protein Bcl‐xL, suggesting that the survival pathway activated by Etoposide involves NF‐kB‐mediated Bcl‐xL expression. Am. J. Hematol., 2006. © 2006 Wiley‐Liss, Inc.