Artemisinin Disrupts Estrogen Receptor-Alpha and Cell GrowthMCF7 cells are an estrogen responsive human breast cancer cell line that expresses both estrogen receptor subtypes, estrogen receptor-alpha (ERa) and estrogen receptor-beta (ERß). Treatment of MCF7 cells with artemisinin (Art), an anti-malarial phytochemical from the sweet wormwood plant, effectively blocked estrogen stimulated cell cycle progression induced by either ß-estradiol (E2), an agonist for both estrogen receptor subtypes, or by propyl pyrazole triol (PPT), a selective ERa agonist. Art strongly down-regulated ERa protein and transcripts without altering expression or activity of ERß. Transfection of MCF7 cells with ERa promoter-linked luciferase reporter plasmids revealed that the Art down-regulation of ERa promoter activity accounted for the loss of ERa expression. Furthermore, Art treatment ablated the estrogenic induction of endogenous progesterone receptor transcripts by either E2 or PPT, and inhibited the estrogenic stimulation of a luciferase reporter plasmid driven by consensus estrogen response elements (ERE). In vitro ERE binding assays revealed that Art treatment resulted in the loss of ERE bound ERa, whereas, the levels of ERE bound ERß were not altered. Treatment of MCF7 cells with a combination of suboptimal combinations of Art and a pure antiestrogen, faslodex resulted in an enhanced reduction of ERa protein levels and in an enhanced G1 cell cycle arrest compared to the effects of either compound alone. Our results show that Art switches proliferative human breast cancer cells from expressing a high ERa:ERß ratio to a condition in which expression of ERß predominates, which parallels the physiological state linked to anti-proliferative events in both normal mammary epithelium and in breast cancer. http://www.cbcrp.org/research/PageGrant.asp?grant_id=4768~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~Artemisia has been used by Chinese herbalists for more than a thousand years in the treatment of many illnesses, such as skin diseases and malaria. The earliest record dates back to 200 BC, in the "Fifty two Prescriptions" unearthed from the Mawangdui Han Dynasty Tombs. Its antimalarial application was first described in Zhouhou Beji Fang ("The Handbook of Prescriptions for Emergencies"), edited in the middle of fourth century by Ge Hong. http://en.wikipedia.org/wiki/ArtemisininSheila, if you had breast cancer, would you avoid an economical safe herb which showed significant cancer prevention (in rats) because BigPharma funded research hadn't given its stamp of approval?Iggie
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