New estrogenic prenylflavone from Epimedium brevicornum inhibits the growth of breast cancer cells.
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 microg/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 microM) of breviflavone B almost eliminated ERalpha 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.
Yap
Sook Peng
SP
Department of Obstetrics and Gynecology, National University of Singapore, Republic of Singapore.
Shen
Ping
P
Butler
Mark S
MS
Gong
Yinhan
Y
Loy
Chong Jin
CJ
Yong
Eu Leong
EL
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D034181:Epimedium; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018515:Plant Leaves; D011960:Receptors, Estrogen / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D011960:Receptors, Estrogen; D004958:Estradiol