Activation of NF-kappa B in murine macrophages by taxol.
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.
Hwang
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Beatrice and Samuel A. Seaver Laboratory, Cornell University Medical College, New York, New York 10021, USA.
Ding
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A
D000818:Animals; D001483:Base Sequence; D005260:Female; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015345:Oligonucleotide Probes / Q000235:genetics; D017239:Paclitaxel / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology
D016328:NF-kappa B; D015345:Oligonucleotide Probes; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D017239:Paclitaxel