Yap Sook Peng, Shen Ping, Butler Mark S, Gong Yinhan, Loy Chong Jin, Yong Eu Leong
Department of Obstetrics and Gynecology, National University of Singapore, Republic of Singapore.
Planta Med. 2005 Feb;71(2):114-9. doi: 10.1055/s-2005-837776.
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.
雌激素维持女性性健康。这种激素还会促使雌激素受体（ER）阳性乳腺肿瘤生长，而诸如他莫昔芬之类的ER调节剂则用于降低肿瘤复发率。为了鉴定可能具有健康益处的植物雌激素，我们对几种中药进行了筛选，发现了一种来自淫羊藿叶的提取物（EB），其具有强烈的（半数有效浓度：1.3微克/毫升）且特异性的ER刺激活性。它在低剂量时会增加雌激素反应性人乳腺癌细胞的增殖，但矛盾的是，在高剂量时会导致生长受到显著抑制。通过生物测定引导的分级分离，我们分离并鉴定了一种新的异戊烯基黄酮——淫羊藿黄酮B，它对乳腺癌细胞增殖具有双相刺激和抑制作用，模拟了EB的作用。与雌二醇和染料木黄酮不同，高剂量（>2微摩尔）的淫羊藿黄酮B几乎消除了ERα蛋白；这一过程可能是通过增加蛋白酶体降解来介导的。需要进行临床前研究来探索这些异戊烯基黄酮在雌激素缺乏状态下以及预防乳腺癌方面是否具有价值。
