Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1990559 | The Journal of Nutritional Biochemistry | 2006 | 6 Pages |
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-α) was identified as a potential molecular target for I3C. Treating MCF-7 cells with 100 μM I3C reduced ER-α mRNA expression by approximately 60% compared to controls. This reduction in ER-α transcript levels was confirmed using real-time polymerase chain reaction. The I3C dimer, 3,3′-diindolylmethane (DIM), was considerably more effective in depressing ER-α mRNA in MCF-7 cells than the monomeric unit. The suppressive effects of 5 μM DIM on ER-α mRNA was comparable to that caused by 100 μM 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, α-naphthoflavone (α-NF, 10 μM) and luteolin (10 μM), to the culture media resulted in a similar suppression in ER-α mRNA levels to that caused by 5 μM DIM. Thus, it is likely that the binding of ligands to AhR inhibits nuclear ER-α 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-α expression through the binding of its metabolite, DIM, to the nuclear AhR.