Breast cancer is the most frequently diagnosed cancer in Western women. Most cases (up to 75%) are estrogen-dependent. The estrogen-independent cases are more invasive, more difficult to treat, and they are connected with worse prognosis. The biologically active estrogens important in the proliferation of breast cancer are produced from inactive precursors by the action of aromatase encoded by CYP19 gene. Conventional treatment (e.i. hormonal therapy) is expensive and for advanced cancer ultimately unsuccessful. That is why early diagnosis and prevention of this disease is urgently needed. A new hope is brought by chemoprevention – the concept of early intervention by usage of different agents inhibiting the development of invasive cancer. Recent epidemiological migrant studies showed that consumption of raw or short cooked cabbage and sauerkraut is connected with significant reduction of breast cancer incidences. Indole-3-carbinol (I3C), 3,3'-diindolylmethane (DIM) – a major in vivo acid-catalyzed condensation product of I3C, and sulforaphane (SUL) are examples of numerous active chemicals in cabbage. The aim of the present study was to investigate the effect of I3C, DIM and SUL on the profile of CYP19 expression in human breast cancer estrogen-dependent MCF-7 cell line. Cells were treated with these compounds at the concentrations relevant to those observed in human plasma. The total RNA extraction from cell cultures after 144 hours of incubation with different substances concentrations and reverse transcriptase reaction preceded the cDNA synthesis. The screening of cDNA from aromatase mRNA was performed using real-time PCR assay. The results showed that I3C in the dose of 30 μM reduced the expression of CYP19 in MCF-7 cell line. In contrast, higher dose of I3C (50 μM) induced its expression. The latter results confirmed the observations of the other authors indicating reciprocal I3C effect on carcinogenesis. SUL in the doses of 5μM and 20μM diminished the level of CYP19 mRNA. Similar trend was observed after treatment with 5 μM and 10 μM of DIM. Since the down-regulation of CYP19 gene causes the reduction in estrogens synthesis the usage of I3C, DIM, and/or SUL could be well-founded as preventive agents against breast carcinoma development. Further investigation on estrogen-independent MDA-MB-231 cell line which is under way are necessary to compare the possible application of I3C, DIM, and SUL as a chemopreventive agents depending on the hormonal character of the tumour.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1113.
Thirty-first San Antonio Breast Cancer Symposium Dec 10-14, 2008; San Antonio, TX