TY - JOUR
T1 - Anethole blocks both early and late cellular responses transduced by tumor necrosis factor
T2 - Effect on NF-κB, AP-1, JNK, MAPKK and apoptosis
AU - Chainy, Gagan B.N.
AU - Manna, Sunil K.
AU - Chaturvedi, Madan M.
AU - Aggarwal, Bharat B.
N1 - Funding Information:
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 IkBa Western blot analysis and with FACS analysis, respectively.
PY - 2000/6/8
Y1 - 2000/6/8
N2 - 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 Iκ-Bα 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.
AB - 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 Iκ-Bα 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.
KW - AP-1
KW - Anethole
KW - Apoptosis
KW - JNK
KW - NF-κB
KW - TNF
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U2 - 10.1038/sj.onc.1203614
DO - 10.1038/sj.onc.1203614
M3 - Review article
C2 - 10871845
AN - SCOPUS:0034622079
SN - 0950-9232
VL - 19
SP - 2943
EP - 2950
JO - Oncogene
JF - Oncogene
IS - 25
ER -