chapter  7
16 Pages

Dietary Factors in Food: Induction of Nrf2-Mediated Defense Genes in Normal Cells versus Inhibition of Cell Growth Genes in Tumor Cells

Cancer Chemopreventive Compounds ..................................................... 191 7.2.1 Isothiocyanates ............................................................................. 192 7.2.2 Polyphenols (Curcumin and EGCG) ............................................ 193

7.3 Regulation of Redox-Sensitive Transcription Factors by Isothiocyanates and Polyphenols ........................................................ 193 7.3.1 Activator Protein-1 (AP-1) ........................................................... 194 7.3.2 Nuclear Factor kappa B (NF-κB) ................................................. 195 7.3.3 Nuclear Factor-E2-Related Factor 2 (Nrf2) ................................. 196

7.4 In Vivo Global Gene Expression Profi les in Response to Isothiocyanates and Polyphenols ......................................................... 197 7.4.1 Phase I, II, and III Xenobiotic Metabolizing

Enzymes/Transporter Genes and Antioxidant Genes Coordinately Regulated via Nrf2 ...................................... 198

7.4.2 Major Clusters of Genes Coordinately Regulated via Nrf2 ......... 199 7.5 Conclusion................................................................................................ 199 Acknowledgments ............................................................................................. 200 References ......................................................................................................... 200

Evolutionarily, animals have been ingesting plants. This “animal-plant” warfare has resulted in an elaborated system of detoxifi cation and defense mechanisms evolved by animals, including humans. Animal cells respond to these dietary phytochemicals by “sensing” this chemical stress typifi ed by “thiol modulated” cellular signaling events leading to gene expression of pharmacologically benefi cial effects but sometimes also unwanted cytotoxicity. Our laboratory has been studying two groups of dietary cancer chemopreventive compounds, isothiocyanates and polyphenols, which are effective against chemical-induced, as well as genetically modifi ed, animal carcinogenesis models [1,2]. These compounds typically generate “cellular stress” and modulate gene expression, including phase II detoxifying/antioxidant enzymes. Indeed, reactive oxygen species (ROS) and reactive nitrogen species (RNS) generated by electrophiles or xenobiotics including these dietary phytochemicals have been proposed as second messengers in the activation of several signaling pathways leading to gene expression responses that are necessary for cell survival and cell death.