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Anethole blocks both early and late cellular responses transduced by tumor necrosis factor: effect on NF-κB, AP-1, JNK, MAPKK and apoptosis


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-κB activation (an early response) as monitored by electrophoretic mobility shift assay, IκBα phosphorylation and degradation, and NF-κB reporter gene expression. Suppression of IκBα phosphorylation and NF-κB reporter gene expression induced by TRAF2 and NIK, suggests that anethole acts on IκBα kinase. Anethole also blocked the NF-κB activation induced by a variety of other inflammatory agents. Besides NF-κB, anethole also suppressed TNF-induced activation of the transcription factor AP-1, c-jun N-terminal kinase and MAPK-kinase. In addition, anethole abrogated TNF-induced apoptosis as measured by both caspase activation and cell viability. The anethole analogues eugenol and isoeugenol also blocked TNF signaling. Anethole suppressed TNF-induced both lipid peroxidation and ROI generation. Overall, our results demonstrate that anethole inhibits TNF-induced cellular responses, which may explain its role in suppression of inflammation and carcinogenesis.

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dihydrorhodamine 123




Fas-associated death domain




inhibitory subunit of NF-κB


IκB-dominant negative


IκBα kinase


electrophoretic mobility shift assay


c-jun amino terminal kinase






mitogen activated protein kinase kinase


nuclear extracts


NF-κB inducing kinase


nuclear transcription factor-κB


okadaic acid


phorbol myristate acetate


poly (ADP) ribose polymerase


TNF receptor-associated death domain


TNF receptor-associated factor 2


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This research was conducted by The Clayton Foundation for Research. We would like to thank Dr B Darnay and Dr NT Van for assistance with IκBα Western blot analysis and with FACS analysis, respectively.

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Chainy, G., Manna, S., Chaturvedi, M. et al. Anethole blocks both early and late cellular responses transduced by tumor necrosis factor: effect on NF-κB, AP-1, JNK, MAPKK and apoptosis. Oncogene 19, 2943–2950 (2000).

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