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Modulation of the Nrf2 Signaling Pathway by Chemopreventive Dietary Phytoconstituents

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Nutrition, Diet and Cancer

Abstract

Epidemiological studies have revealed the healing power of a diet rich in fruits and vegetables in both the prevention and amelioration of chronic illness. Chemoprevention, utilizing dietary agents, has been suggested as a fascinating strategy in the fight against cancer. Dietary phytoconstituents, such as carotenoids, polyphenols and organosulfur compounds, present in a multitude of dietary sources have been shown to possess potent antioxidant and anti-inflammatory properties as well as the ability to modulate a multitude of signaling mechanisms. Oxidative stress is a key element of the pathogenesis of neoplastic diseases and its attenuation is a vital step in the chemopreventive strategy. The nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated signaling pathway is the primary antioxidant mechanism in nature and thus an extremely critical element of the chemopreventive strategy. This chapter highlights the Nrf2-modulating property of dietary phytoconstituents in their ability to afford chemoprevention against a multitude of neoplastic diseases. This article provides a brief explanation of the Nrf-2 signaling pathway, its antioxidant effects and its role in the chemoprevention as well as amelioration of neoplastic disorders. Essentially reviewed are studies which elucidate pharmacological effects of select dietary phytochemicals in pre-clinical models of cancer with special emphasis on their Nrf2 modulating properties. The article also highlights the current status of progress entailed in the development of the Nrf2 modulation pathway using dietary phytonutrients as a robust chemopreventive strategy with practical significance in the clinic.

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Acknowledgments

Our research on chemoprevention of liver cancer by modulation of Nrf2 pathway by several dietary phytoconstituents as described in this chapter was carried out at the Northeast Ohio Medical University (Rootstown, OH) supported by Research Incentive Grant from the Ohio Board of Regents and a New Faculty Start-Up Research Grant to A.B. The authors sincerely thank Animesh Mandal, Ph.D., for assistance with the bibliographic work and Werner J. Geldenhuys, Ph.D., for technical assistance with the illustration (Fig. 20.1).

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  1. Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, OH, 44272, USA

    Altaf S. Darvesh M.Pharm., Ph.D.

  2. Department of Pharmaceutical and Administrative Sciences, School of Pharmacy, American University of Health Sciences, 1600 East Hill Street, Signal Hill, CA, 90755, USA

    Anupam Bishayee

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  1. Altaf S. Darvesh M.Pharm., Ph.D.
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Correspondence to Anupam Bishayee .

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  1. , Pathology and Laboratory Medicine, University of Kansas Medical Center, Rainbow Blvd 3901, Kansas City, 66160, Kansas, USA

    Sharmila Shankar

  2. , Pharmacology and Toxicology, University of Kansas Medical Center, Rainbow Blvd 3901, Kansas City, 66160, Kansas, USA

    Rakesh K. Srivastava

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Darvesh, A.S., Bishayee, A. (2012). Modulation of the Nrf2 Signaling Pathway by Chemopreventive Dietary Phytoconstituents. In: Shankar, S., Srivastava, R. (eds) Nutrition, Diet and Cancer. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2923-0_20

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