Inhibition of NF-kappa B transcription factor by catechol derivatives.

Abstract

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.

• Authors: Y J Suzuki, L Packer
• Journal: Biochemistry and molecular biology international (Biochem Mol Biol Int) Vol. 32 Issue 2 Pg. 299-305 (Feb 1994) ISSN: 1039-9712 [Print] England
• PMID: 8019435 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antioxidants
• Catechol O-Methyltransferase Inhibitors
• Catechols
• Ethers, Cyclic
• NF-kappa B
• Pentanones
• OR 1246
• Okadaic Acid
• nitecapone

Topics

• Antioxidants (pharmacology)
• Base Sequence
• Catechol O-Methyltransferase Inhibitors
• Catechols (pharmacology)
• Ethers, Cyclic (pharmacology)
• Humans
• Leukemia, T-Cell
• Molecular Sequence Data
• NF-kappa B (antagonists & inhibitors)
• Okadaic Acid
• Pentanones (pharmacology)
• Tumor Cells, Cultured