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

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

Ramirez MC, Singletary K.

Department of Food Science and Human Nutrition, University of Illinois, Urbana, 61801, USA.

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 alpha (ERalpha) protein and mRNA in MCF-7 cells. Sulforaphane inhibited cell proliferation with IC(50) values at 24 and 48 h of 12.5 and 7.5 muM doses, respectively, and decreased ERalpha protein expression at concentrations between 2.5 and 30 muM. Inhibition of ERalpha protein expression was also accompanied by decreased progesterone receptor expression. MCF-7 ERalpha mRNA expression was inhibited by SUL at a dose of 30 muM, but not at lower SUL concentrations. At SUL doses <30 muM, the SUL-induced suppression of ERalpha 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, sulforaphane can inhibit the expression of ERalpha protein in MCF-7 cells in part by inhibition of ERalpha mRNA transcription as well as by a mechanism that may involve increased proteasome-mediated degradation. These data provide new insights into mechanisms by which sulforaphane inhibits proliferation of and down-regulates hormone receptor expression in MCF-7 cells.

 

Note from ISS:  Several crucifer sprouts including broccoli sprouts are currently the most potent natural source of sulforaphane known.  They often produce 10 to 100 times the amount of sulforaphane as their corresponding mature vegetables. ("Broccoli sprouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens.", Proc Natl Acad Sci U S A 1997 Sep 16;94(19):10367-72.)