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Vol. 273, Issue 3, 1288-1297, January 16, 1998
From the Extracts from certain Mexican Indian medicinal
plants used in traditional indigenous medicine for the treatment of
inflammations contain sequiterpene lactones (SLs), which specifically
inhibit the transcription factor NF-
Sesquiterpene Lactones Specifically Inhibit Activation of NF-
B
by Preventing the Degradation of IB-
and IB-
,,,, and
Department of Immunochemistry, German Cancer
Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg,
Germany, the § Institute of Pharmaceutical Biology,
Albert-Ludwigs-Universität, Schänzlestrasse 1, 79104 Freiburg, Germany, and the ¶ Medical Clinics, Department of
Internal Medicine I, Otfried-Müller-Str. 10, 72076 Tübingen, Germany
B (Bork, P. M., Schmitz,
M. L., Kuhnt, M., Escher, C., and Heinrich, M. (1997) FEBS
Lett. 402, 85-90). Here we show that SLs prevented the
activation of NF-B by different stimuli such as phorbol esters,
tumor necrosis factor-
, ligation of the T-cell receptor, and
hydrogen peroxide in various cell types. Treatment of cells with SLs
prevented the induced degradation of IB- and IB-
by all
these stimuli, suggesting that they interfere with a rather common step
in the activation of NF-B. SLs did neither interfere with DNA
binding activity of activated NF-B nor with the activity of the
protein tyrosine kinases p59fyn and p60src. Micromolar
amounts of SLs prevented the induced expression of the NF-B target
gene intracellular adhesion molecule 1. Inhibition of NF-B by
SLs resulted in an enhanced cell killing of murine fibroblast cells by
tumor necrosis factor-. SLs lacking an exomethylene group in
conjugation with the lactone function displayed no inhibitory activity
on NF-B. The analysis of the cellular redox state by fluorescence-activated cell sorter showed that the SLs had no direct or
indirect anti-oxidant properties.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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