Cited by 215NF-κB Signaling PathwaysNatural Compounds in Disease TreatmentGenomics, phytochemicals, and oxidative stress

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

Chainy, Gagan BN, Manna, Sunil K, Chaturvedi, Madan M, Aggarwal, Bharat B·2000·Oncogene

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).

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Crossref · 10.1038/sj.onc.1203614

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  • Anethole, eugenol, and isoeugenol inhibit TNF-α-induced NF-κB activation in ML1-a cells.

    “In a short report, Chainy et al. (2000) [148] described that anethole, eugenol and isoeugenol inhibited TNF-α-induced NF-κB activation in ML1-a cells.”
  • Anethole inhibits degradation of IκBα by blocking its phosphorylation in TNF-stimulated ML1-a cells, does not induce MAP kinase phosphorylation, and blocks TNF-induced JNK and AP-1.

    “The same authors also reported that anethole inhibited the degradation of IκBα, blocking its phosphorylation in TNF-stimulated ML1-a cells. In the same cells and with TNF stimulation, anethole did not induce the phosphorylation of MAP kinase. Besides NF-κB and MAP kinase, anethole also blocked TNF-induced JNK and AP-1.”

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Authors
Chainy, G. B., Manna, S. K., Chaturvedi, M. M., & Aggarwal, B. B.
Affiliations
The University of Texas MD Anderson Cancer Center (US)
Venue
Oncogene
Published
2000-06-06
Volume
19
Issue
25
Pages
2943-2950
ISSN
  • 0950-9232 (ISSN-L)
  • 1476-5594
OpenAlex
W2021878174
Cited by
215
References
36
Citations by year
2026: 2 · 2025: 7 · 2024: 15 · 2023: 13 · 2022: 15 · 2021: 9 · 2020: 9 · 2019: 6 · 2018: 4 · 2017: 10 · 2016: 10 · 2015: 12 · 2014: 13 · 2013: 11 · 2012: 18
FWCI
1.35
Type
journal article
Language
en
Open access
closed
Locations
  • Oncogene (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Keywords
anethole, TNF signaling, NF-κB activation, IκBα phosphorylation, IκBα kinase, TRAF2, NIK, AP-1, c-Jun N-terminal kinase, MAPK kinase, apoptosis, caspase activation, eugenol, isoeugenol, lipid peroxidation, reactive oxygen species, inflammation, carcinogenesis, anti-inflammatory agents
MeSH terms
Allylbenzene Derivatives, Anisoles, Cell Line, Flavoring Agents, Transcription Factors, Tumor Necrosis Factor-alpha, Apoptosis, Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase Kinases, JNK Mitogen-Activated Protein Kinases

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