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Oncol Lett. 2016 Nov;12(5):3949-3957. Epub 2016 Sep 28.

Inhibitory effects of Chinese nutritional herbs in isogenic breast carcinoma cells with modulated estrogen receptor function.

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Cancer Prevention Research Program, Palindrome Liaisons Consultants, Montvale, NJ 07645-1559, USA.
American Foundation for Chinese Medicine, New York, NY 1103-0905, USA.
Hampton University Skin of Color Research Institute, Hampton, VA 23668, USA; Department of Dermatology and Leroy T. Canoles Jr Cancer Research Center, Eastern Virginia Medical School, Norfolk, VA 23507, USA.
Hackensack University Medical Center, Hackensack, NJ 07601, USA.
American Foundation for Chinese Medicine, New York, NY 1103-0905, USA; Department of Integrative Medicine, Mount Sinai Beth Israel Medical Center, New York, NY 10003, USA.


In estrogen receptor (ER)+ MCF-7 cells, ER represents a ligand-activated transcription factor, and 17β-estradiol (E2) represents its physiological ligand. Maintenance of the human breast carcinoma-derived MCF-7 cells with 0.7% serum selected a proliferative sub-population of E2-responsive cells with transiently non-functional ER due to limited availability of E2. Culture of MCF-7 cells in the presence of either 0.7% serum, <1 nM E2 or 0.7% serum + 20 nM E2 selected isogenic cells with either non-functional ER (ER-NF) or functional ER (ER-F) phenotype. The two phenotypes responded to the growth-promoting effects of E2 and to the growth-inhibitory effects of the selective ER modulator tamoxifen, indicating retention of E2 responsiveness. Comparative dose-response experiments with Chinese nutritional herbs on ER-NF and ER-F cells identified the inhibitory concentration (IC)50 values for these herbs, while the IC50 ratios for the ER-NF:ER-F phenotypes facilitated their rank ordering in terms of efficacy. Out of the 11 efficacious herbs tested, five herbs exhibited ER-F > ER-NF inhibitory activity, four exhibited ER-F = ER-NF inhibitory activity and two exhibited ER-NF > ER-F inhibitory activity. Extracts from representative herbs, Lycium barbarum bark, Epimedium grandiflorum and Cornus officinalis, from each of the three groups inhibited anchorage-independent growth, induced G1 or G2/M arrest and/or apoptosis, and generated anti-proliferative E2 metabolites. The differential growth inhibition in ER-NF and ER-F phenotypes, together with the mechanistic efficacy of representative herbs, identified potential leads for their efficacy on ER+ and/or ER- breast cancer.


growth inhibition; isogenic breast carcinoma cells; nutritional herbs

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