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Gene expression profiling reveals effects of Cimicifuga racemosa (L.) NUTT. (black cohosh) on the estrogen receptor positive human breast cancer cell line MCF-7.

Gaube F, Wolfl S, Pusch L, Kroll TC, Hamburger M - BMC Pharmacol. (2007)

Bottom Line: 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.The effects may be results of the activation of different pathways.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Pharmacy, Department of Pharmaceutical Biology, University of Jena, Semmelweisstr, 10, 07743 Jena, Germany. Friedemann.Gaube@uni-jena.de

ABSTRACT

Background: 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.

Results: 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.

Conclusion: 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.

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Chemical structure of Actein, the major cycloartane-type triterpene glycoside of black cohosh.
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Figure 1: Chemical structure of Actein, the major cycloartane-type triterpene glycoside of black cohosh.

Mentions: The phytochemicals in black cohosh rhizomes have been well studied, and numerous cycloartane-type triterpene glycosides (e.g. actein Figure 1), aromatic acids (e.g. caffeic and ferulic acid), cinnamic acid esters (e.g. fukinolic acid, cimicifugic acids) and various minor compounds have been reported [1,2,5]. The pharmacology of rhizome extracts has been investigated, whereby most investigations addressed the effects on the hormonal (estrogenic) system. An estrogen-like activity was reported initially [6-8], but these effects could not be confirmed in later studies [8-11]. Subsequently, antiestrogenic properties were proposed on the basis of in vitro experiments [8,12,13]. Because a black cohosh extract influenced bone, endometrium and hypothalamus, but not uterus in a estrogen-like manner, it was postulated to contain compounds that act as selective estrogen receptor modulators (SERMs) and, therefore, to be different from common phytoestrogens – a presumption that is still a matter of dispute [14-17].


Gene expression profiling reveals effects of Cimicifuga racemosa (L.) NUTT. (black cohosh) on the estrogen receptor positive human breast cancer cell line MCF-7.

Gaube F, Wolfl S, Pusch L, Kroll TC, Hamburger M - BMC Pharmacol. (2007)

Chemical structure of Actein, the major cycloartane-type triterpene glycoside of black cohosh.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2194763&req=5

Figure 1: Chemical structure of Actein, the major cycloartane-type triterpene glycoside of black cohosh.
Mentions: The phytochemicals in black cohosh rhizomes have been well studied, and numerous cycloartane-type triterpene glycosides (e.g. actein Figure 1), aromatic acids (e.g. caffeic and ferulic acid), cinnamic acid esters (e.g. fukinolic acid, cimicifugic acids) and various minor compounds have been reported [1,2,5]. The pharmacology of rhizome extracts has been investigated, whereby most investigations addressed the effects on the hormonal (estrogenic) system. An estrogen-like activity was reported initially [6-8], but these effects could not be confirmed in later studies [8-11]. Subsequently, antiestrogenic properties were proposed on the basis of in vitro experiments [8,12,13]. Because a black cohosh extract influenced bone, endometrium and hypothalamus, but not uterus in a estrogen-like manner, it was postulated to contain compounds that act as selective estrogen receptor modulators (SERMs) and, therefore, to be different from common phytoestrogens – a presumption that is still a matter of dispute [14-17].

Bottom Line: 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.The effects may be results of the activation of different pathways.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Pharmacy, Department of Pharmaceutical Biology, University of Jena, Semmelweisstr, 10, 07743 Jena, Germany. Friedemann.Gaube@uni-jena.de

ABSTRACT

Background: 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.

Results: 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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus