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

• Published in: Nutrition and cancer 2009, Vol.61 (3), p.408-414
• Main Authors: Li, Go, Sepkovic, Daniel W, Bradlow, H. Leon, Telang, Nitin T, Wong, George Y.C
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; breast neoplasms; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Line, Tumor; Cell Proliferation - drug effects; estradiol; Estradiol - metabolism; Estradiol - pharmacology; estrogen receptor modulators; estrogen receptor positive breast cancer; estrogens; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gynecology. Andrology. Obstetrics; hormone receptors; human cell lines; Humans; inhibitors; Lycium; Lycium barbarum; Mammary gland diseases; Medical sciences; metabolism; Phytotherapy; plant estrogens; Plant Extracts - pharmacology; Receptors, Estrogen - analysis; Tumors; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0163-5581; 1532-7914
• DOI: 10.1080/01635580802585952

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, E2 < 1 nM) exhibited 11%-87% increased growth after treatment with 1nM to 20 nM E2. Growth promotion with 20 nM E2 exhibited 5.2-fold increased estrone (E1), 35.7% increased 2-hydroxyestrone (2-OHE1), 15.4% increased 16α-hydroxyestrone (16α-OHE1), and eightfold increased estriol (E3) formation. Treatment of E2 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 E1, 3.6-fold increased 2-OHE1, 33.3% decreased 16 -OHE1, and 9.2-fold increased E3 formation. Thus, MCF-7 cells retain their mitogenic and metabolic response to E2 and LB downregulates E2-stimulated growth via the formation of antiproliferative 2-OHE1 and accelerated conversion of mitogenic 16 -OHE1 to antimitogenic E3.