ACTIVATION OF NF-KAPPA-B IN MURINE MACROPHAGES BY TAXOL

Taxol, a plant-derived antimitotic, was recently found to mimic severa l of the effects of endotoxic bacterial lipopolysaccharide on murine m acrophages. However, the mechanisms underlying the cell cycle-independ ent actions of taxol remain unclear. Here, we report that taxol rapidl y activated nuclear factor kappa B (NF-kappa B) in mouse peritoneal ma crophages. The intranuclear transcription factor complexes contained t wo NF-kappa B heterodimers, p50/RelA and p50/c-rel. Taxol-induced nucl ear translocation of NF-kappa B was inhibited by pyrrolidine dithiocar bamate, an antioxidant, but not by cycloheximide, a protein synthesis inhibitor. The ability of taxol to activate NF-kappa B may help accoun t for its induction of immunoregulatory and cytotoxic cytokines, which in turn may contribute to its antitumor effects.