Anethole blocks both early and late cellular responses transduced by tumor necrosis factor: effect on NF-κB, 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).
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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.”
From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [148]
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.”
From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [148]
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Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review
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“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.”
BackgroundCancer cell signaling pathways targeted by spice-derived nutraceuticals
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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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