Gene expression profiles induced by cancer chemopreventive isothiocyanate sulforaphane in the liver of C57BL/6J mice and C57BL/6J/Nrf2 (-/-) mice.
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.
Hu
Rong
R
Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen, Piscataway, NJ 08854, USA.
Xu
Changjiang
C
Shen
Guoxiang
G
Jain
Mohit R
MR
Khor
Tin Oo
TO
Gopalkrishnan
Avantika
A
Lin
Wen
W
Reddy
Bandaru
B
Chan
Jefferson Y
JY
Kong
Ah-Ng Tony
AN
D000818:Animals; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D017879:Isothiocyanates; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D013454:Sulfoxides; D013861:Thiocyanates / Q000737:chemistry / Q000494:pharmacology*; D015533:Transcriptional Activation
D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D013454:Sulfoxides; D013861:Thiocyanates; C016766:sulforaphane