Hormone replacement therapy is contraindicated in women with breast cancer. Extracts from the rhizomes of Cimicifuga racemosa, have gained acceptance as a natural alternative for the treatment of menopausal symptoms. In the present study we investigated the antiproliferative activity of C. racemosa extracts (isopropanolic and ethanolic) on the estrogen receptor positive MCF-7 and estrogen receptor negative MDA-MB231 breast cancer cells by WST-1 assay. Down regulation of the proliferative activity and cell killing by isopropanolic and ethanolic extracts occurred in a clear dose-dependent response with a 50% growth inhibitory concentration of 54.1 +/- 11.4 and 80.6 +/- 17.7 micro g/ml in MCF-7 cells and of 29.5 +/- 3.0 and 58.6 +/- 12.6 microg/ml in MDA-MB231 cells, respectively. Further, the mode of cell death was identified as apoptosis by microscopic inspection and confirmed by light scatter characteristics and by detection of Annexin V adherence to phosphatidylserine by flow cytometry. In addition, the involvement of activated caspases was supported by the cleavage of cytokeratin 18 detected with M30 antibody. Increases in the level of M30-antigen of about 4-fold and 2-fold over untreated controls were observed in C. racemosa -treated MCF-7 and MDA-MB231 cells. These results indicate that C. racemosa extract exerts no proliferative activity, but kills the estrogen receptor positive MCF-7 as well as estrogen receptor negative MDA-MB231 cells by activation of caspases and induction of apoptosis.

The occurrence of vasomotor symptoms in women is directly related to deficiency of estrogen, which occurs as a result of natural or surgical menopause. Hot flushes may also be a major problem for patients with a history of breast cancer, as they may result directly from cancer treatment (oophorectomy, chemotherapy-induced ovarian failure or adjuvant tamoxifen citrate therapy). Despite the lack of reliable data regarding their efficacy and safety, in recent years the usage of herbs among menopausal women has increased dynamically all over the world. The following paper reviews professional literature about Black Cohosh (Actaea/Cimicifuga racemosa), either used alone or in combination with other medicinal herbs administered in management of vasomotor symptoms. Extracts of the rootstock of Black cohosh contain such potentially biologically active constituents as triterpene glycosides (actein, cimicifugoside, deoxyacetein), isoferulic acid and alkaloids (n-methylcytisine). The mechanism of its action remains unclear. Some authors suggest that Black Cohosh contains substances with selective estrogen receptor modulator (SERM) activity. Recent data has demonstrated that Black Cohosh may have an effect on dopaminergic and serotoninergic systems. Thirty-two papers formed the basis for this review. Open-label, noncomparative studies, as well as treatment-controlled, randomized, open trials, have proven that Black Cohosh significantly reduced frequency or severity of hot flashes. The results of randomized, placebo-controlled, double-blind clinical trials were contradictory. Adverse symptoms have been rare (5,4%), mild and reversible. Most of them included gastrointestinal upsets, rashes, headaches, dizziness and mastalgia. Nevertheless, single cases of serious adverse events, including acute hepatocellular damage, have been reported, but without a clear causality relationship.

The Cimicifuga racemosa extract BNO 1055 (CR) inhibits proliferation of human prostate cancer-derived LNCaP cells. Therefore, we tested the capability of this extract to inhibit formation and/or proliferation of tumors induced by subcutaneous ( s. c.) inoculation of LNCaP cells in immunodeficient nu/nu mice. After inoculation of 1 million cells, 12 of 18 animals developed solid tumors while tumor development was seen in only 5 of 18 CR-treated animals and the size of the latter at termination of the experiments 10 weeks after inoculation was significantly smaller than in the control animals. Upon histological inspection, the amount of tumor tissue in the control animals was significantly larger than in the CR-treated animals while in the latter connective tissue was predominant. The CR treatment did not affect serum testosterone levels significantly regardless of whether the animals developed tumors or not. It is concluded that compounds in CR inhibit tumor development, proliferation and dignity of the tumors following s. c. inoculation of LNCaP cells. Hence, the CR extract may prove to be efficient in preventing and treatment of prostate cancer.

Extracts of Cimicifuga racemosa (L.) Nutt. (syn.: Actaea racemosa L.) (CR) inhibit the proliferation of the human prostate cancer cell line LNCaP. Recently, the phenylpropanoid ester 3,4-dihydroxyphenacyl caffeate (petasiphenone, 1) was isolated from CR. This substance is a structural homologue to petasiphenol ([3-(3,4-dihydroxyphenyl)-2-oxopropyl caffeate]), a compound produced by Petasites japonicus Sieb. & Zucc. which inhibits the growth of various human leukemia cell lines. Because of the structural similarity, we examined whether 1 affects the proliferation of LNCaP cells and the secretion of prostate-specific antigen (PSA). Under basal conditions as well as under co-incubation with 10 nM estradiol [E2 or 1 nM dihydrotestosterone (DHT)], 1 dose-dependently inhibited proliferation of LNCaP cells while PSA release per cell was not altered. We report for the first time that a defined compound isolated from CR inhibits the growth of the human prostate cancer cells LNCaP.