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

Abstract 

Sulforaphane [SUL, 1-isothiocyanato-4-(methylsulfinyl)butane] is an isothiocyanate derived from glucoraphanin present in cruciferous vegetables, and it has 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 α (ERα) 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 μM doses, respectively, and decreased ERα protein expression at concentrations between 2.5 and 30 μM. Inhibition of ERα protein expression was also accompanied by decreased progesterone receptor expression. MCF-7 ERα mRNA expression was inhibited by SUL at a dose of 30 μM, but not at lower SUL concentrations. At SUL doses <30 μM, the SUL-induced suppression of ERα 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 ERα protein in MCF-7 cells in part by inhibition of ERα 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.

Keywords: Sulforaphane, Breast cancer, Estrogen receptor, Proteasome, mRNA