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Articles

Indole-3-Carbinol Is a Negative Regulator of Estrogen Receptor- Signaling in Human Tumor Cells¹

Department of Radiation Oncology and ^* Department of Otolaryngology, Long Island Jewish Medical Center, New Hyde Park, NY 11040

²To whom correspondence should be addressed.

Estrogen, via its binding to the estrogen receptor (ER), plays an important role in breast cancer cell proliferation and tumor development. Indole-3-carbinol (I3C), a compound occurring naturally in cruciferous vegetables, exhibits a potent antitumor activity via its regulation of estrogen activity and metabolism. This study was designed to determine the effect of I3C on the potential to inhibit the ER-. Using a reporter gene driven by the estrogen receptor, I3C (10–125 µmol/L) significantly repressed the 17ß-estradiol (E2)-activated ER- signaling in a dose-dependent manner. I3C and breast cancer susceptibility gene 1 (BRCA1) synergistically inhibited transcriptional activity of ER-. Moreover, I3C down-regulated the expression of the estrogen-responsive genes, pS2 and cathepsin-D, and up-regulated BRCA1. The inhibitory effects of I3C did not contribute to its cytotoxic effects because these activities were observed at less than toxic concentrations. These results further suggest that antitumor activities of I3C are associated not only with its regulation of estrogen activity and metabolism, but also its modulation of ER transcription activity.

KEY WORDS: • indole-3-carbinol • estrogen receptor • human breast cancer • breast cancer susceptibility gene 1 (BRCA1)

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