Regulation of Estrogen Receptor Alpha Expression in Breast Cancer Cells by Sulforaphane

Abstract

Sulforaphane (SUL, 1‐isothiocyanato‐4‐(methylsulfinyl) butane) is an isothiocyanate derived from glucoraphanin that is abundant in broccoli and broccoli sprouts and which has a variety of potential chemopreventive actions. SUL is capable of inhibiting cancer at both early (initiation) and late (promotion) stages of experimental tumorigenesis. In this study we analyzed the effects of SUL on proliferation of several human breast cancer cell lines and evaluated the effect of SUL on estrogen receptor alpha (ERα) protein and mRNA expression in MCF‐7 cells. SUL at doses between 10 and 30 μM inhibited proliferation of neoplastic breast cell lines to a greater extent than non‐neoplastic MCF‐10F breast cells. SUL at doses between 2.5 and 30 μM decreased ERα protein expression in MCF‐7 cells. This effect of SUL on ERα expression was apparent under complete and estrogen‐depleted growth conditions and was accompanied by a decrease in progesterone receptor protein expression. At SUL doses of 30μM and greater, SUL treatment was associated with suppression of ERα mRNA transcription. In contrast, at doses of SUL less than 30μM, there was no effect of SUL on ERα mRNA expression. However, the proteasome inhibitor MG132 reversed the suppression of ERα protein levels in MCF‐7 cells treated with SUL at the lower SUL doses. Thus, the downregulation of ERα protein expression appears to be due to multiple dose‐dependent mechanisms involving changes in mRNA expression and proteasome activity. The effect of SUL on hormone‐responsiveness of human breast cancer cells warrants further study.