Application of Pharmacogenomics to Dietary Cancer Chemoprevention

Auemduan      Prawan; Tin      Oo Khor; Wenge      Li; Ah-Ng      Tony Kong

Abstract

Many lines of evidence demonstrate that certain dietary phytochemicals have cancer chemopreventive effects. These dietary phytochemicals or chemo-preventive agents can suppress or block carcinogenesis by (1) enhancing the biotransformation enzymatic activities for efficient elimination of carcinogens or reactive oxidative or nitrosative species (ROS/RNS); (2) suppressing the growth/inflammatory signaling pathways involved in cancer cell proliferation; and (3) modulating phase II detoxifying/antioxidant enzymes, e.g. glutathione S-transferases (GST), NAD(P)H-quinone reductase 1 (NQO1), UDP-glucuronosyltransferases (UGT), and antioxidant enzymes such as gamma-glutamylcysteine synthetase (γ-GCS) and heme oxygenase 1 (HO1). Comparison of gene expression profiles among Nrf2 wild type and Nrf2 knockout mice showed that these genes are induced in an Nrf2-dependent manner in response to phytochemical treatments. The potential roles of different types of polymorphisms or pharmacogenetics in carcinogenesis and prevention/treatment of some of these genes will be described in this review. Finally, the potential usage of these dietary compounds in combination with conventional cancer chemotherapy will also be considered. The applications of pharmacogenomics to dietary cancer chemopreventive studies will be essential for understanding the cancer protective mechanisms and could lead to individualized drug therapies in the future.

Keywords: Pharmacogenomics, microarray, dietary phytochemicals, cancer chemoprevention, Nrf2, signal transduction, gene expression profiles

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