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01.02.2013 | Original Contribution

Ellagic acid coordinately attenuates Wnt/β-catenin and NF-κB signaling pathways to induce intrinsic apoptosis in an animal model of oral oncogenesis

verfasst von: Prabukumar Anitha, Ramamurthi Vidya Priyadarsini, Krishnamurthy Kavitha, Paranthaman Thiyagarajan, Siddavaram Nagini

Erschienen in: European Journal of Nutrition | Ausgabe 1/2013

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Abstract

Purpose

Constitutive activation of the Wnt signaling pathway and its downstream effectors plays a key role in neoplastic transformation. The objective of this study was to investigate the effect of ellagic acid, a plant-derived polyphenol on Wnt/β-catenin signaling and its downstream circuits- NF-κB and mitochondrial apoptosis in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model.

Methods

Hamsters were divided into six groups. The right buccal pouches of animals in groups 1–4 were painted with 0.5% DMBA three times a week for 14 weeks. Animals in groups 2–4 received in addition basal diet containing ellagic acid at a concentration of 0.1, 0.2, and 0.4% in the diet. Group 5 animals were given 0.4% ellagic acid alone. Group 6 animals served as control. The expression of the members of Wnt and NF-κB signaling and intrinsic apoptosis was evaluated by western blot analysis.

Results

Dietary supplementation of 0.4% ellagic acid suppressed the development of HBP carcinomas by preventing the constitutive activation of Wnt pathway through the downregulation of Fz, Dvl-2, GSK-3β and nuclear translocation of β-catenin. Abrogation of Wnt signaling by ellagic acid was also associated with inactivation of NF-κB and modulation of key components of the mitochondrial apoptotic network.

Conclusions

Our findings suggest a functional crosstalk between Wnt and NF-κB signaling pathways in HBP carcinomas that is blocked by ellagic acid supplementation. Dietary ellagic acid that targets the Wnt/β-catenin pathway as well as its downstream signaling mediators is a unique candidate for cancer chemoprevention.

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Titel: Ellagic acid coordinately attenuates Wnt/β-catenin and NF-κB signaling pathways to induce intrinsic apoptosis in an animal model of oral oncogenesis
verfasst von: Prabukumar Anitha
Ramamurthi Vidya Priyadarsini
Krishnamurthy Kavitha
Paranthaman Thiyagarajan
Siddavaram Nagini
Publikationsdatum: 01.02.2013
Verlag: Springer-Verlag
Erschienen in: European Journal of Nutrition / Ausgabe 1/2013
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-011-0288-y

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Ellagic acid coordinately attenuates Wnt/β-catenin and NF-κB signaling pathways to induce intrinsic apoptosis in an animal model of oral oncogenesis

Abstract

Purpose

Methods

Results

Conclusions

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