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

Abstract

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-kappaB activation (an early response) as monitored by electrophoretic mobility shift assay, IkappaBalpha phosphorylation and degradation, and NF-kappaB reporter gene expression. Suppression of IkappaBalpha phosphorylation and NF-kappaB reporter gene expression induced by TRAF2 and NIK, suggests that anethole acts on IkappaBalpha kinase. Anethole also blocked the NF-kappaB activation induced by a variety of other inflammatory agents. Besides NF-kappaB, 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. Oncogene (2000).

• Authors: G B Chainy, S K Manna, M M Chaturvedi, B B Aggarwal
• Journal: Oncogene (Oncogene) Vol. 19 Issue 25 Pg. 2943-50 (Jun 08 2000) ISSN: 0950-9232 [Print] England
• PMID: 10871845 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Allylbenzene Derivatives
• Anisoles
• Flavoring Agents
• Transcription Factors
• Tumor Necrosis Factor-alpha
• JNK Mitogen-Activated Protein Kinases
• Mitogen-Activated Protein Kinases
• Mitogen-Activated Protein Kinase Kinases
• anethole

Topics

• Allylbenzene Derivatives
• Anisoles (pharmacology)
• Apoptosis (drug effects)
• Cell Line
• Flavoring Agents (pharmacology)
• JNK Mitogen-Activated Protein Kinases
• Mitogen-Activated Protein Kinase Kinases (metabolism)
• Mitogen-Activated Protein Kinases (metabolism)
• Transcription Factors (metabolism)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, pharmacology)