Journal
PLANTA MEDICA
Volume 71, Issue 2, Pages 114-119Publisher
GEORG THIEME VERLAG KG
DOI: 10.1055/s-2005-837776
Keywords
Epimedium brevicornum; Berberidaceae; prenylflavone; estrogen; receptor; anti-proliferation; breast; cancer
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Estrogens maintain female sexual health. The hormone also drives the growth of estrogen receptor (ER) positive breast tumors, and ER modulators, like tamoxifen, are used to reduce tumor recurrence. To identify phytoestrogens with possible health benefits, we screened several Traditional Chinese Medicines and encountered an extract from the leaves of Epimedium brevicornum (EB), with strong (EC50: 1.3 mu g/mL) and specific ER-stimulatory activity. It increased estrogen-responsive human breast cancer cell proliferation at low doses, but paradoxically caused profound inhibition,of growth at higher doses. Using bioassay-guided fractionation, we isolated and characterized a new prenylflavone, breviflavone B, which exerted biphasic stimulatory and inhibitory effects on breast cancer cell proliferation, mimicking the effects of EB. In contrast to estradiol and genistein, high doses (> 2 mu M) of breviflavone B almost eliminated ER alpha protein; a process that may be mediated through increased proteasome degradation. Pre-clinical studies are needed to explore whether these prenylflavones are of value in estrogen-deficiency states and for prophylaxis of breast cancer.
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