[Frontiers in Bioscience S3, 1332-1362, June 1, 2011]

Dietary flavonoids as cancer-preventive and therapeutic biofactors

Shin Nishiumi1, Shingo Miyamoto2, Kyuichi Kawabata3, Kohta Ohnishi4, Rie Mukai5, Akira Murakami4, Hitoshi Ashida6Junji Terao5

1Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan, 2Center for Molecular Medicine, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030-3101, USA, 3Department of Bioscience, Fukui Prefectural University, Fukui 910-1195, Japan, 4Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan, 5Department of Food Science, Institute of Health Biosciences, the University of Tokushima Graduate School, Tokushima 770-8503, Japan, 6 Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Kobe 657-8501, Japan

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Epidemiology
4. Absorption and metabolism
5. Chemoprevention (rodent and human studies)
6. Mechanisms
6.1. AhR/transformation
6.1.1. The interaction of flavonoids with AhR
6.1.2. The possibility for the chemoprevention of carcinogenesis through regulation of AhR and/or drug-metabolizing enzymes by flavonoids
6.2. Signal transduction
6.3. Target molecules
7. Potential side-effects
8. Perspectives
9. Acknowledgements
10. References

1. ABSTRACT

Flavonoids are present in many plants, and hence, in foods and ingredients derived from them. These polyphenolic compounds have attracted renewed attention as potential anticarcinogens, and the molecular mechanisms of their anticarcinogenic effects and their bioavailability have been extensively explored. In this review, we focus on the major dietary flavonoids; flavones, flavonols, and flavan-3-ols (catechins), and evaluate their roles in cancer prevention. After absorption with or without metabolic conjugation, flavonoids are transported to target organs where they exert their anticarcinogenic activity. The molecular mechanisms of the anticarcinogenic effects of flavonoids include their antagonistic effect on the aryl hydrocarbon receptor (AhR), and regulation of phase I and II drug metabolizing enzymes and phase III transporters. Experimental evidence suggests that flavonoids modulate signal transduction pathways at each stage of carcinogenesis. The interactions between flavonoids and biomolecules in vivo must be investigated in detail to identify specific targets. In addition, the potential side effects should be considered when flavonoid supplements are used for cancer prevention. Therefore, the use of flavonoids as chemopreventive agents should be further investigated to establish safe levels of flavonoid intake.