Carcinogenesis Advance Access published online on April 16, 2004
Carcinogenesis, doi:10.1093/carcin/bgh169
© 2004 by Oxford University Press
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1 Nutrition Division, Institute of Food Research, Norwich Research Park, Norwich, NR4 7UA, UK
* To whom correspondence should be addressed. E-mail: yongping.bao{at}bbsrc.ac.uk.
The isothiocyanates, sulforaphane and the flavonoid, apigenin modulate gene expression including phase II detoxifying enzymes, such as glutathione transferases (GST) and UDP-glucuronosyltransferases (UGT). Using undifferentiated CaCo-2 cells, we have examined the interactions between sulforaphane and apigenin in the regulation of UGT and GST expression. We show that apigenin induces UGT1A1 transcription (4-fold) but not GSTA1, and that sulforaphane induces both UGT1A1 (3.8-fold) and GSTA1 (2.5-fold) transcription in both dose- and time-dependent manners. The combination of sulforaphane and apigenin resulted in a synergistic induction of UGT1A1 mRNA up to 12-fold, though this interaction was not seen for GSTA1. NF-
Revised March 10, 2004
Accepted April 9, 2004
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Interactions between sulforaphane and apigenin in the induction of UGT1A1 and GSTA1 in CaCo-2 cells
vehlíková 1,
Abstract 
B mRNA was induced by apigenin and sulforaphane (2.5- and 2-fold respectively). NF-B translocation inhibitor SN50 and PI3-kinase inhibitor LY294002 decreased the induction of GSTA1 by sulforaphane almost to baseline level. However, the MEK inhibitor PD98059 enhanced significantly the induction of GSTA1 by sulforaphane. This suggests that NF-B and PI3-kinase signaling pathways play a role in GSTA1 gene expression. Conversely, the induction of UGT1A1 transcription by sulforaphane was totally abolished by PD98059, although PD98059 slightly enhanced (20%) the induction of UGT1A1 by apigenin implying that the induction of UGT1A1 by sulforaphane is mediated by MEK1 ERK, whereas UGT1A1 induction by apigenin may be associated with NF-B translocation since NF-B translocation inhibitor, SN50 enhanced the induction of UGT by apigenin. The results show that UGT1A1 and GSTA1 are regulated by sulforaphane through different signal transduction pathways and the differences in the mechanisms of modulation of UGT1A1 transcription by sulforaphane and apigenin resulted in a synergistic effect between these two compounds in the induction of UGT1A1.
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