Activation of NF-kappa B in murine macrophages by taxol.

Abstract

Taxol, a plant-derived antimitotic, was recently found to mimic several of the effects of endotoxic bacterial lipopolysaccharide on murine macrophages. However, the mechanisms underlying the cell cycle-independent actions of taxol remain unclear. Here, we report that taxol rapidly activated nuclear factor kappa B (NF-kappa B) in mouse peritoneal macrophages. The intranuclear transcription factor complexes contained two NF-kappa B heterodimers, p50/RelA and p50/c-rel. Taxol-induced nuclear translocation of NF-kappa B was inhibited by pyrrolidine dithiocarbamate, an antioxidant, but not by cycloheximide, a protein synthesis inhibitor. The ability of taxol to activate NF-kappa B may help account for its induction of immunoregulatory and cytotoxic cytokines, which in turn may contribute to its antitumor effects.