Pharmacogenetics, Pharmacogenomics and Epigenetics of Nrf2-regulated Xenobioticmetabolizing Enzymes and Transporters by Dietary Phytochemical and Cancer Chemoprevention

Author(s): Tien-Yuan Wu, Tin Oo Khor, Jong Hun Lee, Ka Lung Cheung, Limin Shu, Chi Chen, Ah-Ng Kong.

Journal Name: Current Drug Metabolism

Volume 14 , Issue 6 , 2013


Abstract:

Cancer chemopreventive activities of various phytochemicals have been attributed to the modulation of xenobiotic disposition, which includes absorption, distribution, metabolism, and excretion. The interaction between xenobiotics and xenobiotic-metabolizing enzymes (XMEs) is bidirectional. XMEs are responsible for the biotransformation of xenobiotics such as bioactivation and detoxification. Conversely, xenobiotics affect XMEs through transcriptional regulation (induction or suppression) and post-translational interactions (inhibition or activation). Similar relationships also exist between xenobiotics and their transporters. Studies conducted over the past decade have demonstrated that the transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), plays a critical role in the regulation of detoxifying enzymes and transporters through a signaling system that senses and responds to redox imbalance. The role of Nrf2 in the interaction between chemopreventive phytochemicals and detoxifying enzymes/transporters has become an important topic in cancer chemoprevention. In this review, the genetic and epigenetic factors that contribute to Nrf2-mediated regulation of detoxifying XMEs and transporters are discussed in the context of cancer chemoprevention. Phytochemicals may modulate the genome as well as epigenome, altering the regulation of XMEs and transporters, which may be critical for both cancer chemoprevention and the prevention of other oxidative stress- and inflammatory-related diseases, including cardiovascular, metabolic and neurological pathologies. The pharmacogenomic expression of XMEs and transporters, with an emphasis on both genomics and epigenetics, will also be discussed.

Keywords: Xenobiotic-metabolizing enzymes (XMEs), nuclear factor erythroid 2-related factor 2 (Nrf2), chemoprevention, genetic polymorphism, pharmacogenomics, epigenetics.

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Article Details

VOLUME: 14
ISSUE: 6
Year: 2013
Page: [688 - 694]
Pages: 7
DOI: 10.2174/1389200211314060005
Price: $58

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