Estrogenic Effects of Cimicifuga racemosa (Black Cohosh) in Mice and on Estrogen Receptors in MCF-7 Cells

Abstract

The estrogenic effects of Cimicifuga racemosa or Actacea racemosa (black cohosh, CR) extracts were tested in mice, and their effects on estrogen receptor (ER) levels in human breast cancer MCF-7 cells were also investigated. Four groups of weanling female Kunming mice were given 0 (control), 75, 150, or 300 mg/kg body weight CR extracts orally for 14 days. The estrus cycle and the weights of the uterus and ovary of mice, as well as serum estradiol (E(2)) were measured. The proliferation patterns of MCF-7 cells exposed to CR extracts or 17beta-estradiol were studied by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Subsequently, growth of MCF-7 cells in 0 (control) or 4.75 &mgr;g/L of CR extracts or 0.3 nmol/L of 17beta-estradiol groups were observed for 5 days. ER levels in MCF-7 cells were analyzed by indirect immunofluorescence assay using flow cytometry. The uterine weights of mice increased with the increase in dosage of CR extracts, and the estrus duration was significantly prolonged in the group receiving 300 mg/kg body weight (P <.05). However, CR extracts did not increase the serum E(2) concentration significantly. In the in vitro study, a dose-response relationship was demonstrated when cells were treated with low doses of CR extracts, and the optimal enhancement concentration of CR extracts was 4.75 &mgr;g/L on MCF-7 cells. The doubling times (T(D)) of cell growth in the CR extracts group and the 17beta-estradiol group were 32.1 and 31.7 hours, respectively, both shorter than that of the negative control group (T(D) = 35.3 hours). Additionally, 4.75 &mgr;g/L of CR extracts resulted in significantly increased ER levels compared with the control group (P <.01). In conclusion, CR extracts produced an estrogenic action. The effect of increasing ER levels by CR extracts may be one of the potential mechanisms of its phytotherapeutic effects for postmenopausal symptoms.

A retrospective case–control study of the use of hormone‐related supplements and association with breast cancer

“…21 While many phytoestrogens have proestrogenic properties, and bind the ER with a similar affinity as 17b-estradiol itself, 22 black cohosh may have antiestrogenic effects that inhibit breast carcinogenesis. Black cohosh has been inferred to be antiestrogenic by studies that show a lack of estrogen-induced proliferation of breast cancer cells, 14,15,[23][24][25] showed no competitive binding to ERs nor regulation of estrogeninducible genes, 7 and protected against cellular DNA damage caused by reactive oxygen species by acting as an antioxidant. 26 These data are consistent with the hypothesis that black cohosh may be associated with protection from breast cancer risk.…”

“…However, it is not clear that use of black cohosh or Remifemin would necessarily be associated with the hormonal status of the tumors. Black cohosh has hormonal effects, but its action in terms of breast cancer risk may also be related to its antiproliferative properties, [4][5][6][7][8] which may or may not be independent of hormone receptor status or other hormonal hallmarks of the tumor. Furthermore, it is possible that most breast tumors become estrogen/progesterone sensitive and lose these receptors at a later stage in tumorigenesis.…”

“…It has been proposed that the relatively weaker estrogenic effect of phytoestrogens may compete with that of estradiol and have antiproliferative properties that decrease breast cancer risk. 1,[4][5][6] However, there is also evidence that the estrogenic activity of some of these compounds, including binding to estrogen receptors (ERs), 7,8 may stimulate breast tumor cell proliferation at physiological concentrations, [9][10][11][12] and increase endogenous steroid hormone levels. 13 In addition, estrogenic effects are not consistent across all phytoestrogen-containing compounds.…”

Influence of chronic administration of zearalenone on the processes of apoptosis in the porcine ovary

“…It may be speculated that ZEA, due to its oestrogen-like activity inhibits apoptotic processes in the ovary of intoxicated gilts. This effect might be compared to the action of phytoestrogens from soybean, or Cimicifuga racemosa (Wuttke et al, 2003), showing positive effect in postmenopausal women (Liu et al, 2001). However, it would be not wise to attribute all effects of ZEA to its oestrogenlike activity.…”

Contemporary alternatives to plant estrogens for menopause

“…[26][27][28] However, one study found evidence of estrogenic activity in the urogenital tract of mice. [29] Recent data, in fact, has demonstrated that black cohosh acts on serotonin receptors which may be the mechanism for relief of hot flashes and improvement in mood. [30,31] Much of the research on black cohosh has been conducted in Germany since the 1940's.…”