Pharmacokinetics, Pharmacodynamics and Drug Metabolism

The involvement of Nrf2-a bZip transcription factor in soy isoflavones induced protection against oxidative stress and cancer has been reported. To gain better insight into the role of Nrf2 in prostate cancer chemoprevention by soy isoflavones, we examined the pharmacogenomics and gene expression profiles elicited by soy isoflavones in the prostates of C57BL/6J/Nrf2(−/−) and C57BL6J/Nrf2(+/+) wildtype. The profiles were analyzed using 45000 Affymetrix mouse genome 430-2.0 array and Genespring-7.2 software. The results obtained from microarray were further validated by real-time reverse transcription-PCR. Clusters of genes that were induced or suppressed more than twofold were identified as Nrf2 regulated soy isoflavone induced or suppressed genes. Classification based on their biological function revealed that genes mainly belonging to the categories of electron transport, phase II metabolizing enzymes, cell growth and differentiation, apoptosis, cell cycle, transcription factors, transport, mRNA processing, and carbohydrate homeostasis were either induced or suppressed by soy isoflavone and regulated by Nrf2. In addition, modulation of novel target genes such as LATS2 and GREB1 were identified to be mediated by Nrf2. Thus our current study provides a potential link between cancer chemopreventive properties of soy derived phytochemicals, the transcription factor Nrf2 and prevention of prostate cancer.