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

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Thomas T Y Wang1, Matthew J Milner, John A Milner

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

The Journal of Nutritional Biochemistry
|February 21, 2006
PubMed

Insights

Indole-3-carbinol (I3C) may fight cancer by reducing estrogen receptor alpha (ER-alpha) via its metabolite, 3,3'-diindolylmethane (DIM), which binds to the aryl hydrocarbon receptor (AhR). This mechanism was observed in MCF-7 breast cancer cells.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Nutritional Science

Background:

  • Preclinical studies suggest indole-3-carbinol (I3C) has antitumorigenic properties.
  • The precise molecular mechanisms behind I3C's effects are not fully understood.
  • Estrogen receptor alpha (ER-alpha) is a key factor in many breast cancers.

Purpose of the Study:

  • To investigate the molecular targets of indole-3-carbinol (I3C) in cancer cells.
  • To elucidate the mechanism by which I3C exerts its antitumorigenic effects.
  • To determine the role of estrogen receptor alpha (ER-alpha) in I3C's action.

Main Methods:

  • MCF-7 human breast cancer cells were treated with I3C and its metabolite 3,3 -diindolylmethane (DIM).
  • Estrogen receptor alpha (ER-alpha) mRNA expression was quantified using real-time polymerase chain reaction.
  • The effects of other aryl hydrocarbon receptor (AhR) ligands were assessed.

Main Results:

  • Indole-3-carbinol (I3C) significantly reduced ER-alpha mRNA levels in MCF-7 cells.
  • The I3C metabolite, 3,3 -diindolylmethane (DIM), was more potent than I3C in suppressing ER-alpha mRNA.
  • Aryl hydrocarbon receptor (AhR) ligands, including DIM, inhibited nuclear ER-alpha transcript, suggesting AhR involvement.

Conclusions:

  • The antitumorigenic effects of I3C in MCF-7 cells may be mediated by the reduction of ER-alpha expression.
  • This reduction is likely achieved through the binding of DIM, an I3C metabolite, to the nuclear aryl hydrocarbon receptor (AhR).
  • Targeting ER-alpha via AhR activation presents a potential therapeutic strategy for breast cancer.

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