Regulation of estrogen receptor α expression in human breast cancer cells by sulforaphane

Sulforaphane [SUL, 1-isothiocyanato4-(methylsulfinyl)butane] is an isothiocyanate derived from glucoraphanin present in cruciferous vegetables, and it his a variety of potential chemopreventive actions. We analyzed the effects of SUL on the proliferation of human breast cancer cells and on the expression of estrogen receptor alpha (ER alpha) protein and mRNA in MCF-7 cells. Sulforaphane inhibited cell proliferation with IC50 values at 24 and 48 h of 12.5 and 7.5 mu M doses, respectively, and decreased ER alpha protein expression at concentrations between 2.5 and 30 mu M. Inhibition of ER alpha protein expression was also accompanied by decreased progesterone receptor expression. MCF-7 ER alpha mRNA expression was inhibited by SUL at a dose of 30 mu M, but not at lower SUL concentrations. At SUL doses <30 mu M, the SUL-induced suppression or ER alpha protein was reversed by preincubation with the proteasome inhibitor MG132 and was accompanied by an increase in protein levels of the 20S catalytic core subunit PSMB5. Therefore, SUL can inhibit the expression of ER alpha protein in MCF-7 cells in part by inhibition of ER alpha mRNA transcription as well as by a mechanism that may involve increased proteasome-mediated degradation. These data provide new insights into mechanisms by which SUL inhibits proliferation of and down-regulates hormone receptor expression in MCF-7 cells. (C) 2009 Elsevier Inc. All rights reserved.