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 (17β-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-OHE ₁ ), 15.4% increased 16α -hydroxyestrone (16α -OHE ₁ ), 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-OHE ₁ , 33.3% decreased 16α -OHE ₁ , 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-OHE ₁ and accelerated conversion of mitogenic 16α -OHE ₁ to antimitogenic E ₃ .