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.

In situ levels of oestrogen producing enzymes and its prognostic significance in postmenopausal breast cancer patients.

BACKGROUND: The risk of developing breast cancer is strongly correlated with the overall exposure to oestrogen and most tumours are more or less dependent on oestrogen for their growth. A great majority of breast cancers occur after menopause when the ovaries have ceased to be functional, yet breast tumours in postmenopausal women maintain high intratumoural oestrogen concentrations, primarily through enzymatic conversion of androgenic precursors. PATIENTS: with a hormone dependent tumour generally receive the anti-oestrogen tamoxifen that mediate its anti-tumour effect by competing with oestrogen for binding to the oestrogen-receptor (ER). We therefore propose that the levels of oestrogen producing enzymes may affect the prognosis in postmenopausal breast cancer patients treated with tamoxifen. METHODS: We measured the mRNA and protein levels of aromatase and sulfatase by real-time PCR (n=161) and immunohistochemistry (n=131) in postmenopausal women with breast cancer. RESULTS: A significant better recurrence-free survival was detected in patients with weak or high protein expression of stromal aromatase (P=0.0008), as also demonstrated by a decreased relative risk (RR=0.50, CI=0.33-0.76, P=0.003). When we combined patients with weak and high stromal aromatase and selected only ER-positive patients, the improved prognosis was even more evident (P=0.0000) and was shown to be a significant prognostic factor in a multivariate Cox-model (HR=0.15, CI=0.06-0.39, P=0.000). The mRNA expression of aromatase and sulfatase, as well as the protein expression of sulfatase revealed no prognostic significance. CONCLUSION: Protein expression of stromal aromatase may serve as a significant prognostic marker in ER-positive patients.

Controversies over hormone replacement therapy. HRT as a risk factor of breast cancer in postmenopausal women.

Hormone replacement therapy (HRT) was introduced in order to overcome the problems associated with tissue catabolism to which postmenopausal women are particularly prone. However, it is widely accepted that estrogen is essential for breast tumorigenesis. Therefore, the question is raised as to whether HRT in a long perspective can increase the risk of breast cancer development. Moreover, the results of many observational studies do not fully support the protective effects against e.g., cardiovascular diseases. This mini review summarizes the results of recent studies indicating the benefits and risks related to HTR.