Modulation of the Nrf2 Signaling Pathway by Chemopreventive Dietary Phytoconstituents
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.
KeywordsChemopreventive Agent Organosulfur Compound Nrf2 Pathway Nrf2 Signaling Dietary Agent
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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