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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

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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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Acknowledgments

This work was supported by a grant from the Department of Biotechnology, New Delhi, India under the 7th FP of the Indo-EU Joint Collaborative Project on ‘FUNCFOOD’. We are grateful to Dr. B. Mathavan, Associate Professor of Economics, Annamalai University for help with statistical analysis.

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  1. Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Chidambaram, Tamil Nadu, 608 002, India

    Prabukumar Anitha, Ramamurthi Vidya Priyadarsini, Krishnamurthy Kavitha, Paranthaman Thiyagarajan & Siddavaram Nagini

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  1. Prabukumar Anitha
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  2. Ramamurthi Vidya Priyadarsini
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Correspondence to Siddavaram Nagini.

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Anitha, P., Priyadarsini, R.V., Kavitha, K. et al. Ellagic acid coordinately attenuates Wnt/β-catenin and NF-κB signaling pathways to induce intrinsic apoptosis in an animal model of oral oncogenesis. Eur J Nutr 52, 75–84 (2013). https://doi.org/10.1007/s00394-011-0288-y

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