Pharmacogenomic Profile of Soy Isoflavone Concentrate in the Prostate of Nrf2 Deficient and Wild-Type Mice

• Published in: Journal of pharmaceutical sciences Vol. 97; no. 10; pp. 4528 - 4545
• Main Authors: Barve, Avantika, Khor, Tin Oo, Nair, Sujit, Lin, Wen, Yu, Siwang, Jain, Mohit Raja, Chan, Jefferson Y., Kong, Ah-Ng
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.10.2008; Wiley; American Pharmaceutical Association
• Subjects: Animals; antioxidant response element; Base Sequence; Biological and medical sciences; cancer chemoprevention; DNA Primers; Gene Expression Profiling; General pharmacology; Glycine max - chemistry; Isoflavones - metabolism; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; microarray; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - physiology; Nrf2; Oligonucleotide Array Sequence Analysis; Pharmaceutical technology. Pharmaceutical industry; Pharmacogenetics; pharmacogenomics; Pharmacology. Drug treatments; phase II enzymes; Polymerase Chain Reaction; Prostate - metabolism; prostate cancer; soy isoflavones; cancer chemonrevention; Prostate disease; Genomics; Isoflavone derivatives; Nrf2; Genetics; Male genital diseases; antioxidant response element; Pharmacogenomics; phase II enzymes; Urinary system disease; Pharmaceutical technology; Enzyme; Rodentia; Malignant tumor; Antioxidant; Response element; soy isoflavones; Vertebrata; microarray; Mammalia; Mouse; Animal; Prostate cancer; Prostate; Cancer
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.21311

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. © 2008 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4528–4545, 2008