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J Nutr Biochem. 2006 Oct;17(10):659-64. Epub 2005 Nov 28.

Estrogen receptor alpha as a target for indole-3-carbinol.

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1
Phytonutrients Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USA. wangt@ba.ars.usda.gov

Abstract

A wealth of preclinical evidence supports the antitumorigenic properties of indole-3-carbinol (I3C), which is a major bioactive food component in cruciferous vegetables. However, the underlying molecular mechanism(s) accounting for these effects remain unresolved. In the present study, estrogen receptor alpha (ER-alpha) was identified as a potential molecular target for I3C. Treating MCF-7 cells with 100 microM I3C reduced ER-alpha mRNA expression by approximately 60% compared to controls. This reduction in ER-alpha transcript levels was confirmed using real-time polymerase chain reaction. The I3C dimer, 3,3'-diindolylmethane (DIM), was considerably more effective in depressing ER-alpha mRNA in MCF-7 cells than the monomeric unit. The suppressive effects of 5 microM DIM on ER-alpha mRNA was comparable to that caused by 100 microM I3C. DIM is known to accumulate in the nucleus and is a preferred ligand for aryl hydrocarbon receptor (AhR) to I3C. The addition of other AhR ligands, alpha-naphthoflavone (alpha-NF, 10 microM) and luteolin (10 microM), to the culture media resulted in a similar suppression in ER-alpha mRNA levels to that caused by 5 microM DIM. Thus, it is likely that the binding of ligands to AhR inhibits nuclear ER-alpha transcript. The results from these experiments suggest that the antitumorigenic effects of I3C in MCF-7 human breast cancer cells may arise from its ability to reduce ER-alpha expression through the binding of its metabolite, DIM, to the nuclear AhR.

PMID:
16488130
DOI:
10.1016/j.jnutbio.2005.10.012
[Indexed for MEDLINE]
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