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

Abstract

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. © 2012 The Author(s).