Gene expression profiles induced by cancer chemopreventive isothiocyanate sulforaphane in the liver of C57BL/6J mice and C57BL/6J/Nrf2 (−/−) mice

Hu, Rong; Xu, Changjiang; Shen, Guoxiang; Jain, Mohit R.; Khor, Tin Oo; Gopalkrishnan, Avantika; Lin, Wen; Reddy, Bandaru; Chan, Jefferson Y.; Kong, Ah-Ng Tony

doi:10.1016/j.canlet.2005.11.050

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Volume 243, Issue 2 , Pages 170-192, 18 November 2006

Gene expression profiles induced by cancer chemopreventive isothiocyanate sulforaphane in the liver of C57BL/6J mice and C57BL/6J/Nrf2 (−/−) mice

Rong Hu
- Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen, Piscataway, NJ 08854, USA
- Both authors contributed equally to the presented study.
Changjiang Xu
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen, Piscataway, NJ 08854, USA
- Both authors contributed equally to the presented study.
Guoxiang Shen
- Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen, Piscataway, NJ 08854, USA
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen, Piscataway, NJ 08854, USA
Mohit R. Jain
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen, Piscataway, NJ 08854, USA
Tin Oo Khor
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen, Piscataway, NJ 08854, USA
Avantika Gopalkrishnan
- Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen, Piscataway, NJ 08854, USA
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen, Piscataway, NJ 08854, USA
Wen Lin
- Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen, Piscataway, NJ 08854, USA
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen, Piscataway, NJ 08854, USA
Bandaru Reddy
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen, Piscataway, NJ 08854, USA
- Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen, Piscataway, NJ 08854, USA
Jefferson Y. Chan
- Department of Pathology, University of California, D440 Medical Sciences, Irvine, CA 92697, USA
Ah-Ng Tony Kong
- Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen, Piscataway, NJ 08854, USA
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen, Piscataway, NJ 08854, USA
- Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen, Piscataway, NJ 08854, USA
- Department of Pathology, University of California, D440 Medical Sciences, Irvine, CA 92697, USA
- Corresponding author. Address: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA. Tel.: +1 732 445 3831x228; fax: +1 732 445 3134.

Received 26 June 2005; received in revised form 20 November 2005; accepted 27 November 2005.

Abstract

Sulforaphane (SFN) is a potent and promising naturally occurring dietary cancer chemopreventive compound that exerts its cancer protective effects by the induction of genes including cellular defensive genes such as phase II detoxifying and antioxidant enzymes. This gene induction primarily occurs via the transcription factor Nrf2 acting on the antioxidant response element (ARE) located at the 5′-flanking region of these genes. In the present study, transcriptional expression profiles of the livers obtained from the nrf2 wild-type mice and the nrf2 knockout (−/−) mice after treatments with vehicle or SFN at 3 and 12h were generated using the Affymetrix 39K oligonucleotide microarray. The Nrf2-dependent, SFN-inducible genes were identified which include detoxification phase I, II drug metabolizing enzymes and phase III transporters. Unexpected clusters of genes include genes for heat shock proteins (HSP), ubiquitin/26S proteasome subunits, and lipid metabolism genes. Collectively, SFN increases the expression of genes through the Nrf2 signaling pathway that directly detoxify exogenous toxins/carcinogens or endogenous reactive oxygen species, and genes involved in the recognition and repair/removal of damaged proteins, which could provide secondary protection against DNA or protein damage that enhance cell survival.