Lycium Barbarum Inhibits Growth of Estrogen Receptor Positive Human Breast Cancer Cells by Favorably Altering Estradiol Metabolism

Selective estrogen receptor modulators represent accepted therapy for estrogen receptor positive (ER+) breast cancer, exhibit adverse side effects, and reduce patient compliance. The use of phytoestrogen containing herbal medicines is limited because of efficacy and safety concerns. The ER+ MCF-7 model examined growth inhibitory effects of the medicinal herb Lycium barbarum (LB) and identified mechanistic leads for its efficacy. The MCF-7 cells maintained in 0.7% serum (17 beta-estradiol, E-2 < 1 nM) exhibited 11%-87% increased growth after treatment with 1nM to 20 nM E-2. Growth promotion with 20 nM E-2 exhibited 5.2-fold increased estrone (E-1), 35.7% increased 2-hydroxyestrone (2-OHE1), 15.4% increased 16 alpha-hydroxyestrone (16 alpha-OHE1), and eightfold increased estriol (E-3) formation. Treatment of E-2 stimulated cells with LB exhibited a dose-dependent growth inhibition of 9.5%-42.8% at Day 3 and 33.9%-83.9% at Day 7. The 3-day inhibitory response to 1% LB (maximum cytostatic concentration) exhibited 84.8% increased E-1, 3.6-fold increased 2-OHE1, 33.3% decreased 16 alpha-OHE1, and 9.2-fold increased E-3 formation. Thus, MCF-7 cells retain their mitogenic and metabolic response to E-2 and LB downregulates E-2-stimulated growth via the formation of antiproliferative 2-OHE1 and accelerated conversion of mitogenic 16 alpha-OHE1 to antimitogenic E-3.