Volume 97, Issue 10 pp. 4528-4545

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

Avantika Barve

Avantika Barve

Graduate Program in Pharmaceutical Sciences, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854

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Tin Oo Khor

Tin Oo Khor

Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854

Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854

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Sujit Nair

Sujit Nair

Graduate Program in Pharmaceutical Sciences, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854

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Wen Lin

Wen Lin

Graduate Program in Pharmaceutical Sciences, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854

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Siwang Yu

Siwang Yu

Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854

Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854

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Mohit Raja Jain

Mohit Raja Jain

Department of Biochemistry and Molecular Biology, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, New Jersey 07013

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Jefferson Y. Chan

Jefferson Y. Chan

Department of Pathology, University of California, D440 Medical Sciences, Irvine, California 92697

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Ah-Ng Kong

Corresponding Author

Ah-Ng Kong

Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854

Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854

Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854 Telephone: 732-445-3831 ext. 228; Fax: 732-445-3134Search for more papers by this author
First published: 30 January 2008
Citations: 5

Abstract

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

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