Gaube Friedemann, Wolfl Stefan, Pusch Larissa, Kroll Torsten C, Hamburger Matthias
Institute of Pharmacy, Department of Pharmaceutical Biology, University of Jena, Semmelweisstr, 10, 07743 Jena, Germany.
BMC Pharmacol. 2007 Sep 20;7:11. doi: 10.1186/1471-2210-7-11.
Extracts from the rhizome of Cimicifuga racemosa (black cohosh) are increasingly popular as herbal alternative to hormone replacement therapy (HRT) for the alleviation of postmenopausal disorders. However, the molecular mode of action and the active principles are presently not clear. Previously published data have been largely contradictory. We, therefore, investigated the effects of a lipophilic black cohosh rhizome extract and cycloartane-type triterpenoids on the estrogen receptor positive human breast cancer cell line MCF-7.
Both extract and purified compounds clearly inhibited cellular proliferation. Gene expression profiling with the extract allowed us to identify 431 regulated genes with high significance. The extract induced expression pattern differed from those of 17beta-estradiol or the estrogen receptor antagonist tamoxifen. We observed a significant enrichment of genes in an anti-proliferative and apoptosis-sensitizing manner, as well as an increase of mRNAs coding for gene products involved in several stress response pathways. These functional groups were highly overrepresented among all regulated genes. Also several transcripts coding for oxidoreductases were induced, as for example the cytochrome P450 family members 1A1 and 1B1. In addition, some transcripts associated with antitumor but also tumor-promoting activity were regulated. Real-Time RT-PCR analysis of 13 selected genes was conducted after treatment with purified compounds - the cycloartane-type triterpene glycoside actein and triterpene aglycons - showing similar expression levels compared to the extract.
No estrogenic but antiproliferative and proapoptotic gene expression was shown for black cohosh in MCF-7 cells at the transcriptional level. The effects may be results of the activation of different pathways. The cycloartane glycosides and - for the first time - their aglycons could be identified as an active principle in black cohosh.
总状升麻根茎提取物作为激素替代疗法（HRT）的草药替代品，在缓解绝经后紊乱方面越来越受欢迎。然而，目前其分子作用模式和活性成分尚不清楚。先前发表的数据大多相互矛盾。因此，我们研究了一种亲脂性总状升麻根茎提取物和环阿尔廷烷型三萜类化合物对雌激素受体阳性人乳腺癌细胞系MCF-7的影响。
提取物和纯化化合物均明显抑制细胞增殖。用提取物进行基因表达谱分析使我们能够鉴定出431个具有高度显著性的调控基因。提取物诱导的表达模式不同于17β-雌二醇或雌激素受体拮抗剂他莫昔芬。我们观察到以抗增殖和凋亡敏感方式显著富集的基因，以及编码参与几种应激反应途径的基因产物的mRNA增加。这些功能组在所有调控基因中高度富集。还诱导了几种编码氧化还原酶的转录本，例如细胞色素P450家族成员1A1和1B1。此外，一些与抗肿瘤但也与肿瘤促进活性相关的转录本受到调控。用纯化化合物——环阿尔廷烷型三萜糖苷actein和三萜苷元——处理后，对13个选定基因进行实时RT-PCR分析，结果显示与提取物相比表达水平相似。
在转录水平上，总状升麻在MCF-7细胞中未表现出雌激素作用，而是具有抗增殖和促凋亡基因表达。这些作用可能是不同途径激活的结果。环阿尔廷烷糖苷及其苷元首次被确定为总状升麻的活性成分。
