Inhibition of NF-kappa B transcription factor by catechol derivatives.
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.
Department of Molecular & Cell Biology, University of California, Berkeley 94720.
Y J
YJ
Suzuki
L
L
Packer
D000975:Antioxidants / Q000494:pharmacology*; D001483:Base Sequence; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology; D006801:Humans; D015458:Leukemia, T-Cell; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D019319:Okadaic Acid; D010422:Pentanones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004988:Ethers, Cyclic; D016328:NF-kappa B; D010422:Pentanones; C088170:OR 1246; D019319:Okadaic Acid; C057364:nitecapone