Gbn. Chainy et al., Anethole blocks both early and late cellular responses transduced by tumornecrosis factor: effect on NF-kappa B, AP-1, JNK, MAPKK and apoptosis, ONCOGENE, 19(25), 2000, pp. 2943-2950
Anethole, a chief constituent of anise, camphor, and fennel, has been shown
to block both inflammation and carcinogenesis, but just how these effects
are mediated is not known, One possibility is TNF-mediated signaling, which
has also been associated with both inflammation and carcinogenesis. In the
present report we show that anethole is a potent inhibitor of TNF-induced
NF-kappa B activation (an early response) as monitored by electrophoretic m
obility shift assay I kappa B alpha phosphorylation and degradation, and NF
-kappa B reporter gene expression. Suppresaon of I kappa B alpha phosphoryl
ation and NF-kappa B reporter gene expression induced by TRAF2 and NIK, sug
gests that anethole acts on I kappa B alpha kinase, Anethole also blocked t
he NF-kappa B activation induced by a variety of other inflammatory agents.
Besides NF-kappa B, anethole also suppressed TNF-induced activation of the
transcription factor AP-1, c-jun N-terminal kinase and MAPK-kinase, In add
ition, anethole abrogated TNF-induced apoptosis as measured by both caspase
activation and cell viability. The anethole analogues eugenol and isoeugen
ol also blocked TNF signaling. Anethole suppressed TNF-induced both lipid p
eroxidation and ROI generation. Overall, our results demonstrate that aneth
ole inhibits TNF-induced cellular responses,,which mag explain its role in
suppression of inflammation and carcinogenesis.