Modulation of CYP19 expression by cabbage juices and their active components: indole-3-carbinol and 3,3′-diindolylmethene in human breast epithelial cell lines

PURPOSE The aim of this study was to evaluate the effect of white cabbage and sauerkraut juices of different origin and indole-3-carbinol (I3C) and diindolylmethane (DIM) on expression of CYP19 gene encoding aromatase, the key enzyme of estrogen synthesis. METHODS Human breast cell lines (MCF7, MDA-MB-231 and MCF10A) were examined to compare the action of cabbage juices versus their active components (I3C, DIM). Real-time PCR and Western blot were used in order to analyse CYP19 mRNA and protein, respectively. RESULTS Remarkable differences in the effect on CYP19 transcript and protein level were found between the cabbage juices (in 2.5-25 mL/L concentrations) and indoles (in 2.5-50 μM doses) in the three cell lines. While cabbage juices at the lower doses diminished the aromatase expression in nontumorigenic/immortalized MCF10A breast cells (0.25-0.86-fold change, P < 0.05), I3C and DIM were more efficient in decreasing the aromatase expression in estrogen-dependant MCF7 breast cancer cells (0.24-0.82-fold change, P < 0.05). Inhibition of aromatase by juice obtained from cabbage grown on industrial farm was correlated with the induction of apoptosis (1.7-1.8-fold change, P < 0.01) in MCF10A cells. In estrogen-independent MDA-MB-231 cells, up-regulation of CYP19 expression by I3C and DIM (1.5-2.0-fold change, P < 0.05) was observed. Similarly, in MCF7 cells juices increased aromatase expression (1.1-2.2-fold change, P < 0.05). CONCLUSION These results, particularly that obtained in nontumorigenic/immortalized MCF10A cells, suggest that chemopreventive activity of cabbage against breast cancer observed in epidemiological studies may be partly explained by inhibition of the aromatase expression.