Thomas T. Y. Wanga, Matthew J. Milnerb, John A. Milnerc, Young S. Kimc. — Phytonutrients Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USA; b — Department of Biology, The Pennsylvania State University, University Park, PA, USA; c — Nutritional Science Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
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-a) was identified as a potential molecular target for I3C. Treating MCF-7 cells with 100 AM I3C reduced ER-a mRNA expression by approximately 60% compared to controls. This reduction in ER-a transcript levels was confirmed using real-time polymerase chain reaction. The I3C dimer, 3,3V-diindolylmethane (DIM), was considerably more effective in depressing ER-a mRNA in MCF-7 cells than the monomeric unit. The suppressive effects of 5 AM DIM on ER-a mRNA was comparable to that caused by 100 AM 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, a-naphthoflavone (a-NF, 10 AM) and luteolin (10 AM), to the culture media resulted in a similar suppression in ER-a mRNA levels to that caused by 5 AM DIM. Thus, it is likely that the binding of ligands to AhR inhibits nuclear ER-a 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-a expression through the binding of its metabolite, DIM, to the nuclear AhR.
Keywords: Indole-3-carbinol; 3,3V-Diindolylmethane; Estrogen receptor A.
Просмотреть и скачать публикацию (файл в формате PDF, 245 КБ).