Document 0164
 DOCN  M9480164
 TI    Inhibition of NF-kappa B transcription factor by catechol derivatives.
 DT    9410
 AU    Suzuki YJ; Packer L; Department of Molecular & Cell Biology, University
       of California,; Berkeley 94720.
 SO    Biochem Mol Biol Int. 1994 Feb;32(2):299-305. Unique Identifier :
       AIDSLINE MED/94290341
 AB    Therapeutic agents which target NF-kappa B transcription factor may be
       useful in the management of AIDS, cancer and inflammation. Since
       oxidative stress has been implicated in the signaling pathway, the use
       of antioxidants to inhibit NF-kappa B activation has gained attention.
       In the present study, we examined the effects of catechol derivatives,
       nitecapone and OR-1246, which have been identified to possess potent
       antioxidant properties, on NF-kappa B activation by monitoring its DNA
       binding activity. Both nitecapone and OR-1246 (10-300 microM) inhibited
       NF-kappa B activation induced by tumor necrosis factor-alpha in Jurkat T
       (acute human leukemia) cells. Nitecapone was a better inhibitor than
       OR-1246. The observed effects may, at least in part, be due to the
       ability of the two compounds to directly inhibit DNA binding activity of
       activated NF-kappa B. The inhibitory capability of OR-1246 on NF-kappa B
       DNA binding does not appear to be a sole mechanism, as it did not
       inhibit NF-kappa B activation induced by okadaic acid. Hence, catechol
       derivatives inhibit NF-kappa B transcription factor through multiple
       mechanisms, and nitecapone and OR-1246 may be useful as therapeutic
       agents targeting NF-kappa B.
 DE    Antioxidants/*PHARMACOLOGY  Base Sequence  Catechol
       Methyltransferase/ANTAGONISTS & INHIB  Catechols/*PHARMACOLOGY
       Comparative Study  Ethers, Cyclic/PHARMACOLOGY  Human  Leukemia, T-Cell
       Molecular Sequence Data  NF-kappa B/*ANTAGONISTS & INHIB
       Pentanones/*PHARMACOLOGY  Support, Non-U.S. Gov't  Support, U.S. Gov't,
       P.H.S.  Tumor Cells, Cultured  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).