Anethole Blocks Both Early and Late Cellular Responses Transduced by Tumor Necrosis Factor: Effect on NF-kappaB, AP-1, JNK, MAPKK and Apoptosis

Oncogene. 2000 Jun 8;19(25):2943-50. doi: 10.1038/sj.onc.1203614.

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

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